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Introduction
Gram Positive bacterium has been renowned as a pathogen of hospitals acquired infectious. One among these bacteria is Enterococcus species. Enterococcus species are ubiquitous, commensally inhabitants of the gastrointestinal tract of humans and animals. These can be frequently isolated from the environmental sources such as soil, surface water, raw plant and animal products. Even these can screen from female genital tract, oropharynx and skin. Enterococcus sps belongs to the gram positive, facultative anaerobic cocci with an optimum growth temperature of 35°C [1]. There are around 36 species of enterococci have been reported; conversely 26 species are associated with human infection. The most predominant human pathogen is Enterococcus faecalis, even Enterococcus faecium is one of the important pathogen which is prevalent increasing as hospital acquired infections. The other remaining enterococci species only accounts 5% of infections [2, 3, 4]. Some few examples of enterococcus species which are associated with human infections, E. avium, E. cecorum, E. cassseliflavus, E. durans, E. gallinarum, E. raffinosus [5, 6].
E. faecalis has now become the most common nosocomial pathogen and its virulence is increasing in clinical isolates. The presence and function of different suggested characteristics related virulence have been reported [7, 8]. The factor which influences the virulence is mediated through gelatinase production, enterococcus surface protein (ESP), aggregation substance (AS), and biofilm formation [9]. It cause the following infections such as pelvic and abdominal infections, infections in the mouth especially after root canal surgery, infections in open wounds, a lesser known form of meningitis called enterococcal meningitis, infections in the blood called bacteremia and urinary tract infections.
Biofilms are surface attached, organized microbial communities made up of sessile cells (bacteria and /or fungi) embedded in an extracellular matrix composed of polysaccharides, DNA and other components.
2. Chronological background on biofilm
Generally bacterial cell grow in two modes; biofilm formation through aggregate and planktonic cell. It associated with microorganism in which cells stick to each other on a surface encased within matrix of extracellular polymeric substance produced by bacteria itself [10]. Antoni van Leeuwenhoek, the Dutch research, who discovered the simple microscope and observed ‘animalcule’ on surfaces of tooth and this event is known as discovery of biofilm. Characklis, in the year 1973 phrase that biofilms are not only tenacious but even resist to disinfectants (e.g. chlorine). In 1978, Costerton, defined the term biofilm and explained the importance of biofilm. Biofilms can be found in nature in all places like waste water, labs, and hospital settings. It forms as floating mat on the surface of liquid on both living and non-living surfaces [11].
3. Components of biofilm
Biofilm are produced from different group of organisms, the microbes cells produces the extracellular polymeric substances (EPS) such as DNA <1%, Polysaccharides 1–2%, proteins(includes enzymes) with <1–2%, RNA <1% and water with 97% are the major part of biofilm which is responsible for the flow of nutrients inside biofilm matrix [12]. The main two components of the biofilm that is water channel for nutrients transport and a region of densely packed cells having no prominent pores in it [12]. Another way microbial cells in which biofilms are arranged with significant different physiology and physical properties. They will access of antibiotics and human immune system. The organism that produces biofilm has capability to bear and neutralize antimicrobial agents and result in prolonged treatment. The bacteria which produces the biofilm, switch on the genes that can activate the expression of stress genes which in turn switch to resistant phenotypes due to certain changes examples are as follows cell density, nutritional, temperature, pH and osmolarity. When the biofilm water channels are compared with system of circulations showed that biofilms are considered primitive multi-cellular organism [13, 14]. The compositions of biofilms like DNA, proteins, polysaccharides and water will signify the biofilm integrity and making it resistant against different environmental factors [15].
4. Epidemiology of biofilm formation by Enterococcus faecalis
In the worldwide, the prevalence of production of biofilm varies to different part. The study reported in Rome, Italy, 80% of E. faecalis isolates have ability to form biofilms in the infected patients [16]. In India, a study has showed that 52% of E. faecalis isolated screened from clinical samples has showed the biofilm formation [17]. In China, Shenzhen Nanshan Hospital, the prevalence of E. faecalis biofilm formation has showed 50.4% (57/113) in urinary tract infection isolates [18]. The biofilm formation in case of food isolates were less with 60% non-biofilm producers. The major ability in formation of biofilm was endodontic isolates with 73.7% was observed in the Department of Operative Dentistry and Periodontology, University of Freiburg Medical Center, Germany [19].
A study carried out Ahvaz teaching hospital, Iran demonstrated that high frequency 63% of biofilm formation in clinical isolates [20]. The E. faecalis bacterial isolated from patient with complicated UTI from department of Urology, Okayama University, Japan has showed the biofilm formation 64 (18.2%) and 156 (44.3%) exhibited strong and medium respectively [21]. A study reported at Malaysia, the E. faecalis isolates has showed the biofilm formation of 49% [22]. In the United Kingdom, 100% E. faecalis isolates produced biofilms, these isolates were from intravascular catheter-related bloodstream infections (CRBI) found to produce more biofilm than enterococcal isolates that cause non-CRBI [23]. A 93% of E. faecalis strains isolated from clinical samples especially fecal isolates have showed more biofilm formation in the United States [24]. In Spain, 57% of E. faecalis clinical isolates represent the biofilm production [25]. Tertiary care hospital in India showed 26% isolates of E. faecalis having capability in forming biofilm [26].
5. Pathogenesis of biofilm in causing disease
Generally infectious is connected with biofilm primarily confine to particular location and though time detachment may occur. Further, the detached biofilms may result in bloodstream or urinary tract infections or in the production of blockage of blood flow [26]. In another side cells in biofilms are mostly resistant to antimicrobial agents and the host immune system. E. faecalis isolates which produces biofilms is 1000 times more resistant to antibodies, antimicrobial agents and phagocytosis process than non-biofilm producers. Consequently, infections caused from E. faecalis associated with biofilm aggravated in this case [27, 28].
In endocarditis infection a complex biofilm formed by E. faecalis and host components will be formed on cardiac valve. These biofilms causes disease is through three basic mechanisms. Firstly, the biofilms physically disrupts valve function and may cause leakage. Second, detachment of biofilm can be carried to a terminal point in the circulation and formation of emboli (blockage of the blood vessel). Finally, the biofilm provides continuous infection of the bloodstream even during antibiotic treatment. These can cause recurrent fever, chronic systemic inflammation and lead to other infection also [27, 29].
6. Mechanism steps involved in E. faecalis biofilm formation
It comprises of four stages; initial attachment, microcolony formation, biofilm maturation (which is in part governed by quorum sensing) and dispersal.
7. Initial attachment
A surface adhesion is the first step in establishing a biofilm, and a number of surface adhesions, proteases, and lipids are involved. The endocarditis and biofilm-associated pilus (Ebp), which is composed of subunits A, B, and C, mediates the adherence of biofilms on surface in-vitro and in-vivo [30, 31, 32, 33, 34, 35]. The deletion of ebpABC attenuates binding to platelets, fibrinogen and collagen, reduces initial attachment, and thus impairs biofilm formation in-vitro [30, 32, 33].
In addition, Ebp contributed to early biofilm formation in in-vivo models of urinary tract infection (UTI), catheter associated UTI (CAUTI), and infectious endocarditis, in which bacteria with deletions of pilus components were substantially attenuated [30, 32, 33, 36]. Additionally, the absence of surface adhesions, such as aggregation substance (Agg), enterococcol surface protein (ESP), and adhesion to collagen from E. faecalis (Ace), reduced adhesion to cultured human cells and prevented biofilm formation in-vivo [37, 38, 39, 40, 41]. Bacteria deficient for Esp showed reduced initial attachment and decreased bladder colonization in a UTI ascending model, which is not unexpected since Esp binds fibrinogen and collagen, and these ligands are present in the bladder because Esp binds fibrinogen and collagen, and these ligands are present in the bladder [41, 42].
Ace is also involved in interacting with collagen, laminin, and dentin and deletion of Ace resulted in reduced colonization in rat endocarditis and UTI models [43, 44, 45, 46, 47]. As a result, Ace deletion in the peritonitis model did not reduce bacterial burden suggesting Ace-mediated biofilm formation is not relevant to peritoneal infection. By disparity, deletion of Agg reduced adherence to renal epithelial cells [38, 39], binding to lipoteichoic acid (LTA) of other E. faecalis cells (and therefore inter-bacterial clumping) and bacterial titers recovered from endocarditis vegetation on aortic heart valves. Agg cannot colonize the urinary tract, suggesting that Agg-mediated biofilms aren’t necessary for ascending UTI’s [48, 49].
In-vitro, biofilm associated glycolipid synthesis A (BgsA) contributes to initial adhesion and biofilm development, but its role in-vivo is unknown [50]. The extracellular secreted protein encoded by salB (Saga-Like Protein B) increased fibronectin and collagen binding but decreased biofilm formation paradoxically, which has hypothesized to be owing to the salB mutant cells decreased hydrophobicity. These investigations suggest that a variety of variables play a role in the initial attachment of bacteria, and that their contribution is likely to vary depending on the surface to which the bacteria adhere. As a result, focusing on a single component as anti-adherence or anti-biofilm strategy is unlikely to totally prevent enterococcal biofilm formation [37].
8. Microcolony formation
Bacteria proliferate and produce modest amounts of biofilm matrix to form aggregates known as microcolonies after first adhesion [51]. However, the enterococcal mechanisms that drive the establishment of microcolonies are unknown, and no transcriptome data from early-stage biofilms or microcolonies is available. The importance of microcolonies for gut colonization has been demonstrated. E. faecalis colonization of the stomach of germ free mice resulted in discrete microcolonies covered in a fibrous sweater-like matrix within a week, rather than the largely 2D biofilm sheets (2–3 cells high) that are normally observed in biofilm models in-vitro [52].
Despite the fact that microcolonies are commonly assumed to be a temporary stage of early biofilm production, these data imply that microcolonies may represent a mature biofilm stage in this niche that is particularly crucial for gut colonization. In addition, in-vitro enterococcal microcolonies emerge in response to antibiotic therapy [53, 54]. Biofilms treated with sub-inhibitory levels of daptomycin began to restructure extensively into microcolonies as early as 8 hours after drug exposure, in contrast to typical biofilm sheets. Even in the absence of antibiotics, deletion mutants of eapOX, which encodes a glycosyl-transferase involved in the formation of cell wall associated rhamnopolysaccharide (Epa), developed microcolonies in-vitro. In contrast to the monolayer biofilms, these epaOX microcolonies had lower structural integrity, as shown by their facile separation following washing.
9. Biofilm growth and maturation
Active growth and synthesis of extracellular matrix components such as extracellular DNA (eDNA), polysaccharides, LTA, and extracellular proteases are required for biofilm development. eDNA is the best studied matrix component of enterococcal biofilms:eDNA can be found at the bacterial septum, as part of intercellular filamentous structures, and as part of the larger biofilm matrix, and its release from cells is controlled by autolysin Atla [55, 56, 57].
eDNA-associated cells showed no significant cell lysis and had a membrane potential [55], implying that eDNA is liberated from metabolically active cells. As a result, DNase treatment decreased biofilm stability and increased detachment [58, 59], whereas atlA deletion decreased eDNA release and biofilm formation [56]. Despite the lack of evidence that eDNA influences the spatial organization of enterococcal biofilms (as has been postulated for other bacterial species), eDNA remains a potential therapeutic target.
Biofilm production is also aided by non-proteinaceous cell surface components such as glycoproteins, polysaccharides, and modified lipids. The dltABCD operons are involved in the production of D-alanine esters of LTA, which are an important component of Gram-positive bacteria’s cell wall, and deletion of this operons decreased biofilm formation in-vitro, decreased adherence to epithelial cells, and increased susceptibility to antimicrobial peptides [60]. Biofilm on plastic D (BopD), a potential sugar-binding transcriptional regulator, also promotes to biofilm development in-vitro [61].
The deletion of bopABC, which is located upstream of bopD, boosted biofilm growth in glucose but decreased biofilm growth and colonization levels in the murine gut, implying that the ability to utilize maltose is required for biofilm growth in the gut. MprF2, a paralogue of multiple peptide resistance factor (MprF), was likewise found to promote eDNA release and biofilm formation [61, 62, 63]. MprF2 reduces the net positive charge of the membrane via aminoacylating phosphatidylglyceroal to mediate electrostatic repulsion of cationic antimicrobial peptides.
While deletion of MprF2 had no effect on biofilm persistence in a mouse bacteremia model, deletion of both MprF1 and MprF2 reduced biofilm persistence in a wound infection model, suggesting that cell membrane charge may play a role in biofilm formation and pathogenicity in-vivo [63, 64]. These findings back up the theory that cell surface glycoproteins, membrane phosphatidylglycerol, and polysaccharides all play a role in biofilm development.
The quorum sensing response regulator FsrA regulates matrix remodeling by upregulating the expression of gelE, SprE, and altA [57, 58, 65, 66, 67]. The proteases gelE and sprE were found to diminish biofilm formation in-vitro and bacterial load in numerous in-vivo models [68, 69, 70, 71]. However, in a rabbit endocarditis model, loss of gelE alone increased fibrinous matrix formation in aotic vegetation, leading to endocarditis as shown in the Table 1 [70].
Name of the Gene | Gene code | Role |
---|
D-alanine- d-alanine ligase | ddl | It involved in metabolism process (d-ala) especially for bacterial peptidoglycan biosynthesis. Its role in cell wall integrity and biofilm formation. |
Cytolysin | cyl | It a secreted toxin expressed in response to pheromones, contributes to the pathogenicity of E. faecalis by causing blood hemolysis. |
Gelatinase | gelE | It hydrolyzes the gelatin and ability to damage host tissues plays a vital role in spreading of enterococci in their host. It promotes the aggregation of the cells in microcolonies which constitutes the initial step of biofilm formation. |
Serine protease | sprE | It hydrolyzes the casein, quorum sensing and autolysis (release of eDNA) |
Fecal streptococci regulator locus genes | fsrA, fsrB, fsrC | It the major quorum sensing in E. faecalis, the fsr regulator locus, is encoded by fsrA, fsrB and fsrC genes which regulate the expression of both gelatinase and serine protease. It controls biofilm development through regulating the production of gelatinase. |
Biofilm associated pili | ebp | It is the protein organelles, anchored to the surface of the bacterium, that interact with the external environment. It role in biofilm formation, initial attachment and IE. |
Adhesion to collagen of E. faecalis | ace | A surface protein that facilitates the bacterial adherence to collagen is the adhesion to collagen of E. faecalis. It play key role in adherence and colonization process. |
Aggregation substance | agg | A surface protein expressed in response to pheromone induction that mediates the adherence of E. faecalis to renal epithelial cells. It plays important role in adherence to and colonization of host tissues. |
Enterococcal fibronectin-binding protein A | efbA | It is an adhesin, localized on the outer surface of E. faecalis that confers adhesion to immobilized fibronectin. |
Enterococcal surface protein | esp | It promotes primary attachment and biofilm formation. |
LuxS/autoincuder −2 (AI-2) quorum sensing system | luxS | It plays role in interspecies communication and involved in bacterial virulence, persistence infections and biofilms |
Table 1.
Different quorum sensing genes signaling molecules involved in Enterococcus quorum sensing system and virulence factors production.
In-vitro, sprE deletion increased autolysis and eDNA release and accelerated biofilm development, but gelE deletion inhibited eDNA releaseand elevated ace expression, which may increase surface attachment but make the biofilm detachable [71, 72].
10. Quorum sensing
Population density-dependent signaling influences biofilm formation [73, 74]. Despite the fact that quorum sensing and peptide pheromone signaling are known to coordinate gene expression and direct enterococcus biofilm growth, there have been few research on these tiny signaling molecules and secondary messengers in enterococci. The cCF10 peptide pheromone, which facilitates the transfer of the conjugative plasmid pCF10, is an exception. This plasmid has the ability to transfer antibiotic resistance genes as well as virulence determinants like Agg across cells [75, 76, 77, 78, 79]. The buildup of cCF10, which stimulates conjugation proteins, is required for pCF10 transfer. The mechanism underpinning peptide pheromone-mediated gene regulation and plasmid transfer has been well documented, and it was recently demonstrated in mice to promote pCF10 transmission between E. faecalis cells in the gut [79, 80]. The immature peptide pheromones cAD1 and cCF10 are processed by the membrane protease Eep. Eep also facilities the proteolytic processing of RsiV, the anti-sigma factor for sigV, resulting in improved stress resistance. A sigV mutant showed similar symptoms, indicating that Eep is involved in the regulation of sigV production [81, 82, 83].
In-vitro, Eep, together with AhrC and the ArgR family transcriptional regulators, leads to biofilm formation, and deletion of the genes encoding either protein lowered bacterial burden in UTI and endocarditis models [84, 85, 86]. Furthermore, eep deletion mutants develop tiny aggregates unlike wild-type biofilms. FsrABC is another quorum-sensing system. FsrC is a membrane sensor kinase that detects density-dependent accumulation of the FsrB peptide and triggers a signal to the FsrA response regulator [87]. Because this system controls multiple biofilm-related genes and operons (such as bopABCD, ebpABC, GelE, and SprE), knocking down fsrABC entirely eliminates biofilm formation [88]. FsrD, a precursor for the cyclic peptide gelatinase biosynthesis activating pheromone (GBAP), is also controlled by the Fsr quorum sensing system as shown in the Table 1 [89]. Finally, autoinducer 2 (Al-2) is involved in E. faecalis biofilm formation and is produced by S-ribosylhomocysteinelyase (LuxS). In-vitro biofilm development of E. faecalis is increased by Al-2 supplementation, while luxS deletion causes aberrant biofilm production with aggregation a dense structure, in contrast to the confluent monolayers of wild type in-vitro biofilms [90, 91].
11. Factors influencing for the formation of biofilms in E. faecalis
11.1 Dlt gene
A Lipoteichoic Acid, component of E. faecalis, the most common organism in root canals, develops colonies on the dentin surface (LTA). LTA is a biofilm-forming component of E. faecalis that functions as a receptor molecule on receptor cells during the aggregation process. E. faecalis antigen recognizes immune cells via pattern recognition receptors (PRRs) and induces the release of proinflammatory cytokines like TNF alpha (TNFα), interleukin 1 beta (IL-1β), IL-6, and IL-8 [92]. LTA causes cells to produce cytokines, which is followed by the activation of Nuclear Factors kβ (NF-kβ), which promotes cytokines release as shown in the Table 2 [93].
Factors | Function |
---|
dlt gene | It as acts biofilm forming component during aggregation process. It causes cells to produce cytokines. It controls cationic homeostasis and autolytic activity |
Cytolysin lytic enzymes | It is the virulence factors, play role in lysing erythrocytes and collagen fragmentation. The cylLL and cylLS genes on cytolysin promoted for longer survive of E. faecalis. |
Hyaluronidase | It acts as toxin protein for the progression of host tissue increase damage and inflammation. It beneficial protein for the development of E. faecalis. |
Dentine Matrix | It increases the enhancement of biofilm formation through dentin. It also resists the antimicrobial treatment by delay penetration of the drug through the biofilm matrix by altering/changing the physiological shaper of biofilm growth in dentin. |
Nutrients | Glucose is the major determinate in the formation of E. faecalis. It utilizes as the carbon source and hydrolyzes the substrate for its survival. |
Environmental | Physicochemical properties of the surface may exert a strong influence on the rate and extent of attachment. Temperature, cations, and presence of antimicrobial agents influence the attachment. The optimum temperature 37°C, pH -8.5 increase the production biofilm formation. |
Table 2.
Factors influencing for the formation of biofilms in E. faecalis.
The release of these cytokines causes the dlt gene in LTA to fabricate D-alanine instantly, causing other bacteria to assist in the formation of biofilms [94, 95]. The D-Ala-LTA gene is triggered by the surface protein of Gram-Positive bacteria. Cationic homeostasis and autolytic activity are controlled by this gene. Additionally, it is involved in the assimilation of metal cations as well as the electromechanical repair of bacterial cell walls [94]. These capabilities will enhance bacterial cell system transfer while even increasing autolytic activity. The host’s defense system will be weakened by the modified tick.
11.2 Cytolisin lytic enzymes
A lytic enzyme operated on by cytolysin is the one of E. faecalis bacteria’s virulence factors. Apart from lysing erythrocytes, collagen fragmentation caused by this enzyme can cause tissue injury at the site of inflammation. The cylLL and cylLs genes on cytolysin promote this role, allowing E. faecalis to survive longer. E. faecalis is the most common microbe found in root canals [92, 96]. Other bacteria will be inhibited by E. faecalis cytolysin. The cylLL and cylLS genes in E. faecalis cytolysin encode structural cytolysin subunits. They create cytolysin in anaerobic circumstances and respond to oxygen depletion in root canals by producing cytolysin as shown in the Table 2.
11.3 Hyaluronidase
Hyaluronidase is a protein to be found in E. faecalis that helps the bacteria and toxins progress to the host tissue. Other bacteria will continue to migrate from the root canal to the periapical lesions as a result of hyaluronidase. Furthermore, hyaluronidase stimulates the production of toxins by other bacteria, which increases damage and inflammation. This stipulation is very beneficial for the development of E. faecalis [97, 98].
11.4 Dentine matrix structurization
E. faecalis will increase resistance to antimicrobial treatments by increasing the biofilm structural characteristics at the primary site of E. faecalis invasion, notably dentin. As a result, E. faecalis is known to delay antimicrobial agent penetration through the biofilm matrix by altering the growth rate of other microbes in biofilm development and encouraging changes in the physiological shape of biofilm growth in dentin.
When E. faecalis is cultivated in nutrient-poor media, it forms thicker biofilms than when cultured in nutrient-rich media [99]. Under stress inducing mechanism in other bacteria that can cause a more resilient E. faecalis biofilm. Besides E. faecalis biofilms profitably renew themselves. Furthermore, E. faecalis will receive vital carbon by hydrolyzing the substrate required for survival [23].
E. faecalis will continue to grow and develop in environments with or without oxygen with extreme alkaline pH by penetrating cell membrane ions and increasing the cytoplasmic’s buffer capacity [100]. The pH balance of the biofilm is always maintained by bacteria by assimilation of protons into the cell, resulting in a lower internal cell pH. As a result, the dentin buffer capacity is unable to keep the pH in the dentinal tubule constant, and E. faecalis survives [101].
Other investigations found in E. faecalis that the ability to promote apatite re-deposition in the forming biofilm is responsible for its persistence after root canal therapy. Besides this, the dentin matrix is composed of chlorapatite Ca5 (PO4)3 [102]. Different varieties of apatite have different dissolving tolerances. Till date, chlorapatite has been considered as a weaker apatite than hydroxyapatite and fluorapatite in terms of nanostructure [102, 103]. Although it is known that calcium hydroxide can stimulate the formation of hard tissue by raising the Ca2+ ion to increase defense through dentin mineralization, the type of apatite that makes up the host dentin will influence the results [104, 105].
However, no further research into the drug resistance of this inorganic dentin material’s nanostructures has been done. Furthermore, dentin deterioration is not solely dependent on inorganic elements. Collagen makes up 20% of the organic dentin, which accounts for 85% of the total [103]. Gelatinase, an E. faecalis virulence component, is required for hydrolyzing host collagen, High gelatinase levels have been linked to dentin organic matrix degradation [106, 107].
11.5 Tolerance for antimicrobial therapy
Antimicrobial therapy is known to be limited to eliminating free microbes but not to remove cells bound to the biofilm so that re-infection can occur [100]. As a root canal medication, calcium hydroxide is currently the most popular option among dentists. E. faecalis is known to be resistant to calcium hydroxide. This is a serious clinical problem. Every root canal treatment failure, which is documented widely, has linked to E. faecalis [101]. Calcium hydroxide is known to prevent the acid reaction that happens as a result of the inflammatory response. This lactic acid generated by osteoclasts to absorb hard tissue will be neutralized by the alkaline pH [102, 103].
12. Conclusion
Enterococcus faecalis is one of the most predominant organism in nosocomial infection and also developed the drug resistance. The intrinsic virulence factors E. faecalis are associated in biofilm formation and other environmental factor and signals are alarming the biofilm formation. A genome wide study is required to know the role of genetic and environmental factors in development of biofilm and mounting the superior strategies for biofilm control in E. faecalis isolates.
\n',keywords:"biofilm, Enterococcus faecalis, pathogenesis, microcolony, quorum sensing",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81571.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81571.xml",downloadPdfUrl:"/chapter/pdf-download/81571",previewPdfUrl:"/chapter/pdf-preview/81571",totalDownloads:30,totalViews:0,totalCrossrefCites:0,dateSubmitted:"January 21st 2022",dateReviewed:"February 25th 2022",datePrePublished:"April 29th 2022",datePublished:null,dateFinished:"April 29th 2022",readingETA:"0",abstract:"Enterococci are commensal bacteria in the gastrointestinal flora of animals and humans. These are an important global cause of nosocomial infections. A Biofilm formation constitutes an alternative lifestyle in which microorganisms adopt a multi-cellular behavior that facilitates and prolongs survival in diverse environmental niches. The species of enterococcus forms the biofilm on biotic and abiotic surfaces both in the environment and in the healthcare settings. The ability to form biofilms is among the prominent virulence properties of enterococcus. The present chapter highlights the mechanisms underlying in the biofilm formation by enterococcus species, which influences in causing development of the diseases.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81571",risUrl:"/chapter/ris/81571",signatures:"Ajay Kumar Oli, Palaksha K. Javaregowda, Apoorva Jain and Chandrakanth R. Kelmani",book:{id:"11092",type:"book",title:"Bacterial Biofilms",subtitle:null,fullTitle:"Bacterial Biofilms",slug:null,publishedDate:null,bookSignature:"Dr. Theerthankar Das",coverURL:"https://cdn.intechopen.com/books/images_new/11092.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-796-0",printIsbn:"978-1-80355-795-3",pdfIsbn:"978-1-80355-797-7",isAvailableForWebshopOrdering:!0,editors:[{id:"179493",title:"Dr.",name:"Theerthankar",middleName:null,surname:"Das",slug:"theerthankar-das",fullName:"Theerthankar Das"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Chronological background on biofilm",level:"1"},{id:"sec_3",title:"3. Components of biofilm",level:"1"},{id:"sec_4",title:"4. Epidemiology of biofilm formation by Enterococcus faecalis",level:"1"},{id:"sec_5",title:"5. Pathogenesis of biofilm in causing disease",level:"1"},{id:"sec_6",title:"6. Mechanism steps involved in E. faecalis biofilm formation",level:"1"},{id:"sec_7",title:"7. Initial attachment",level:"1"},{id:"sec_8",title:"8. Microcolony formation",level:"1"},{id:"sec_9",title:"9. Biofilm growth and maturation",level:"1"},{id:"sec_10",title:"10. Quorum sensing",level:"1"},{id:"sec_11",title:"11. Factors influencing for the formation of biofilms in E. faecalis",level:"1"},{id:"sec_11_2",title:"11.1 Dlt gene",level:"2"},{id:"sec_12_2",title:"11.2 Cytolisin lytic enzymes",level:"2"},{id:"sec_13_2",title:"11.3 Hyaluronidase",level:"2"},{id:"sec_14_2",title:"11.4 Dentine matrix structurization",level:"2"},{id:"sec_15_2",title:"11.5 Tolerance for antimicrobial therapy",level:"2"},{id:"sec_17",title:"12. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'[Murray BE. The life and times of the Enterococcus. 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Gelatinase contributes to the pathogenesis of endocarditis caused by Enterococcus faecalis. Infection and Immunity. 2010;78:4936-4943]'},{id:"B72",body:'[Thomas VC, Thurlow LR, Boyle D, Hancock LE. Regulation of autolysis dependent extracellular DNA release by Enterococcus faecalis extracellular proteases influences biofilm development. Journal of Bacteriology. 2008;190:5690-5698]'},{id:"B73",body:'[Pinkston KL et al. The Fsr quorum- sensing system of Enterococcus faecalis modulates surface display of the collagen- binding MSCRAMM ace through regulation of gelE. Journal of Bacteriology. 2011;193:4317-4325]'},{id:"B74",body:'[Krasteva PV, Giglio KM, Sondermann H. Sensing the messenger: The diverse ways that bacteria signal through c- di-GMP. Protein Science. 2012;21:929-948]'},{id:"B75",body:'[Camilli A, Bassler BL. Bacterial small moleculesignaling pathways. Science. 2006;311:1113-1116]'},{id:"B76",body:'[Cook LC, Federle MJ. 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MBio. 2018;9:e00037-e00018]'},{id:"B82",body:'[An FY, Sulavik MC, Clewell DB. Identificationand characterization of a determinant (eep) on the Enterococcus faecalis chromosome that is involvedin production of the peptide sex pheromone cAD1. Journal of Bacteriology. 1999;181:5915-5921]'},{id:"B83",body:'[Chandler JR, Dunny GM. Characterization of the sequence specificity determinants required forprocessing and control of sex pheromone by the intramembrane protease Eep and the plasmid encoded protein PrgY. Journal of Bacteriology. 2008;190:1172-1183]'},{id:"B84",body:'[Varahan S, Iyer VS, Moore WT, Hancock LE. Eep confers lysozyme resistance to Enterococcusfaecalis via the activation of the extracytoplasmic function sigma factor SigV. Journal of Bacteriology. 2013;195:3125-3134]'},{id:"B85",body:'[Frank KL et al. AhrC and Eep are biofilm infectionassociatedvirulence factors in Enterococcus faecalis. Infection and Immunity. 2013;81:1696-1708]'},{id:"B86",body:'[Frank KL et al. Evaluation of the Enterococcus faecalis biofilm associated virulence factors AhrC and Eep in rat foreign body osteomyelitis and in vitro biofilm associated antimicrobial resistance. PLoS One. 2015;10:e0130187]'},{id:"B87",body:'[Frank KL et al. Use of recombinase based in vivoexpression technology to characterize Enterococcus faecalis gene expression during infection identifiesin vivo- expressed antisense RNAs and implicates the protease Eep in pathogenesis. Infection and Immunity. 2012;80:539-549]'},{id:"B88",body:'[Ali L et al. Molecular mechanism of quorum- sensingin Enterococcus faecalis: Its role in virulence and therapeutic approaches. International Journal of Molecular Sciences. 2017;18:960]'},{id:"B89",body:'[Hancock LE, Perego M. The Enterococcus faecalis fsr two- component system controls biofilm developmentthrough production of gelatinase. Journal of Bacteriology. 2004;186:5629-5639]'},{id:"B90",body:'[Nakayama J et al. Revised model for Enterococcus faecalis fsr quorum sensing system: The small open reading frame fsrD encodes the gelatinase biosynthesis activating pheromone pro-peptide corresponding to staphylococcal agrd. Journal of Bacteriology. 2006;188:8321-8326]'},{id:"B91",body:'[Shao C et al. LuxS dependent AI-2 regulates versatile functions in Enterococcus faecalis V583. Journal of Proteome Research. 2012;11:4465-4475]'},{id:"B92",body:'[He Z et al. Effect of the quorum- sensing luxS gene on biofilm formation by Enterococcus faecalis. European Journal of Oral Sciences. 2016;124:234-240]'},{id:"B93",body:'[Kayaoglu G, Orstavik D. Virulence factors of Enterococcus faecalis: Relationship of endodontic disease. Critical Reviews in Oral Biology and Medicine. 2004;15(5):308-320]'},{id:"B94",body:'[Albiger B, Dahlberg S, Henriques-Normark B, Normark S. Role of the innate immune system in host defence against bacterial infections: Focus on the toll-like receptors. Journal of Internal Medicine. 2007;261:511-528]'},{id:"B95",body:'[Neuhaus FC, Baddiley J. A continuum of anionic charge: Structures and functions of D-alanyl-teichoic acids in gram-positive bacteria. Microbiology and Molecular Biology Reviews. 2003;67:686-723]'},{id:"B96",body:'[Fabretti F, Theilacker C, Baldassarri L, Kaczynski Z, Kropec A, Holst O, et al. Alanine esters of enterococcal lipoteichoic acid play a role in biofilm formation and resistance to antimicrobial peptides. Infection and Immunity. 2006;74:4164-4171]'},{id:"B97",body:'[Distel JW, Hatton JF, Gillespie MJ. Biofilm formation in medicated root canals. Journal of Endodontia. 2002;28:689-693]'},{id:"B98",body:'[Abou-Rass M, Bogen G. Microorganisms in closed periapical lesions. International Endodontic Journal. 1998;31:39-47]'},{id:"B99",body:'[Sunde PT, Olsen I, Debelian GJ, Tronstad L. Microbiota of periapical lesions refractory to endodontic therapy. Journal of Endodontia. 2002;28:304-310]'},{id:"B100",body:'[Shin SJ, Lee JI, Baek SH, Lim SS. Tissue levels of matrix metalloproteinases in pulps and periapical lesions. Journal of Endodontia. 2002;28:313-315]'},{id:"B101",body:'[Athanassiadis B, Abbott PV, Walsh LJ. The use of calcium hydroxide, antibiotics and biocides as antimicrobial medicaments in endodontics. Australian Dental Journal. 2007;52(1 Suppl):S64-S82]'},{id:"B102",body:'[Evan M, Davies JK, Sundqvist G, Fidgor D. Mechanisms involved in the resistance of the Enteococcus faecalis to calcium hydroxide. International Endodontic Journal. 2002;35:221-228]'},{id:"B103",body:'[Nasution AI, Soraya C, Nati S, Alibasyah ZM. Effect of ethylene diamine tetra acetic acid and rcprep to microstrain of human root dentin. Journal of International Oral Health. 2016;8(1):32-33]'},{id:"B104",body:'[Avery JK, Chiego DJ. Essential of Oral histology and embryology. In: A Clinical Approach. 3rd ed. Missouri: Mosby Elsevier; 2006. pp. 108-113]'},{id:"B105",body:'[Cwikla S, Bellanger M, Giguere S, Fox A, Verticci F. Dentinal tubulus disinfection using three calcium hydroxide formulation. Journal of Endodontia. 2000;31:50-52]'},{id:"B106",body:'[Estrella C, Pimenta FC, Ito IY, Bamman LL. Antimicrobial evaluation of calcium hydroxide in infected dentinal tubules. Journal of Endodontia. 1999;25:416-418]'},{id:"B107",body:'[Tjaderhane L, Palosaari H, Wahlgren J, Larmas M, Sorsa T, Salo T. Human odontoblast culture method: The expression of collagen and matrix metalloproteinases (MMPs). Advances in Dental Research. 2001;15:55-58]'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Ajay Kumar Oli",address:"ajay.moli@hotmail.com",affiliation:'- Department of Biomedical Science, SDM Research Institute for Biomedical Sciences, Shri Dharmasthala Manjunatheshwara University, India
'},{corresp:null,contributorFullName:"Palaksha K. Javaregowda",address:null,affiliation:'- Department of Biomedical Science, SDM Research Institute for Biomedical Sciences, Shri Dharmasthala Manjunatheshwara University, India
'},{corresp:null,contributorFullName:"Apoorva Jain",address:null,affiliation:'- Department of Biomedical Science, SDM Research Institute for Biomedical Sciences, Shri Dharmasthala Manjunatheshwara University, India
'},{corresp:null,contributorFullName:"Chandrakanth R. Kelmani",address:null,affiliation:'- Department of Biotechnology, Gulbarga University, India
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\n\nIn order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\n\n\n\t- Does your institution already have a budget for covering Open Access publication costs?
\n\t- Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\n
\n\nIf you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
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This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 24th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:31,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:43,paginationItems:[{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82212",title:"Protein Prenylation and Their Applications",doi:"10.5772/intechopen.104700",signatures:"Khemchand R. 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Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. 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He is especially interested in the genetic differentiation pattern and speciation process that correlate to the flashing pattern and mating behavior of some fireflies in Japan. He then worked for Olympus Corporation, a Japanese manufacturer of optics and imaging products, where he was involved in the development of luminescence technology and produced a bioluminescence microscope that is currently being used for gene expression analysis in chronobiology, neurobiology, and developmental biology. 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Changes in the environment caused by human activity accelerate the impoverishment of biodiversity.
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\r\n\r\n\tBiodiversity provides food security and constitutes a gene pool for biotechnology, especially in the field of agriculture and medicine, and promotes the development of ecotourism.
\r\n\r\n\tCurrently, biologists admit that we are witnessing the first phases of the seventh mass extinction caused by human intervention. It is estimated that the current rate of extinction is between a hundred and a thousand times faster than it was when man first appeared. The disappearance of species is caused not only by an accelerated rate of extinction, but also by a decrease in the rate of emergence of new species as human activities degrade the natural environment. The conservation of biological diversity is "a common concern of humanity" and an integral part of the development process. Its objectives are “the conservation of biological diversity, the sustainable use of its components, and the fair and equitable sharing of the benefits resulting from the use of genetic resources”.
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Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 24th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:314,numberOfPublishedBooks:31,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/185684",hash:"",query:{},params:{id:"185684"},fullPath:"/profiles/185684",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()