Open access peer-reviewed chapter

Psuedomonas aeruginosa-Associated Acute and Chronic Pulmonary Infections

Written By

Nazish Mazhar Ali, Safia Rehman, Syed Abdullah Mazhar, Iram Liaqat and Bushra Mazhar

Submitted: September 6th, 2019 Reviewed: July 29th, 2020 Published: December 9th, 2020

DOI: 10.5772/intechopen.93504

From the Edited Volume

Pathogenic Bacteria

Edited by Sahra Kırmusaoğlu and Sonia Bhonchal Bhardwaj

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Pseudomonas aeruginosa is highly successful in colonizing in all types of environments. P. aeruginosa colonizing in adverse environment due to the presence of its virulence factors include production of toxins, proteases hemolysins, and formation of biofilms. In man, the most common opportunist pathogen is P. aeruginosa. Metabolically P. aeruginosa is versatile. Most of the antibiotics targeted metabolically active cells and bacteria could contribute to decrease in biofilm susceptibility to the antimicrobial agents. Scientists suggested about Pseudomonas that it can be catabolized any hydrocarbon in specific time along with availability of oxygen and nitrite. If bacteria are not susceptible to one agent in three or more, it is called as multidrug-resistance strains. The antimicrobial treatments were not suitable when microorganism presented in vitro microorganism resistance to antimicrobials used for treatment of the patient which lack of treatment for 24 h after diagnosis of microbial infections. Bacteria have developed resistance against commonly used antibiotics. Treatment of Pseudomonas infections is coming harder day by day as its resistance against most of the antibiotics. Because of resistance of bacteria antibiotics, alternative methods are in consideration. These methods include use of lactic acid bacteria (LAB) and most recently nano-particles. That is why they are used as antibacterial agents.


  • P. aeruginosa
  • pulmonary infections
  • acute lung infections
  • cystic fibrosis
  • quorum sensing system
  • virulent genes
  • antibacterial agents
  • LAB

1. Introduction

P. aeruginosa contributes its pathogenicity onwards respiratory infections in the hospitalized patients. Dasenbrook et al. has reported two types of airways infection acute and chronic spread by hospital community P. aeruginosa is a bacterium that lives in versatile environments [1]. It is Gram negative bacterium, metabolically able to regulate its systems and highly resistance to antibiotic causing it to spread in diverse habitats mainly in hospitals. P. aeruginosa is recognized as a human adaptable pathogen causing acute infections (bacteremia, pneumonia and urinary tract infections) in individuals with HIV infections, surgical wounds, cancer, carrying catheters or burns, or an organ transplantations. P. aeruginosa is persistence in chronic obstructive pulmonary diseases and chronic infections in individuals with cystic fibrosis (CF) [3, 4]. P. aeruginosa strains showed variation in their population as reported by characterization of the phenotypic clones. Four main clade of P. aeruginosa population are identified by the phylogenic analysis of single nucleotide polymorphisms (SNPs) which showed most different clade colonized by clonal outliers linked to the PA7 strain (Figure 1) [5].

Figure 1.

P. aeruginosa features relevant to pathogenicity and adaptation [2].


2. Virulence factors

Acute infection usually observed in hospitalized patients having ventilator breathing. It is one of the main causative agents of hospital-acquired pneumonia and causing morbidity and mortality in the infected patients. Chastre and Fagon has reported 70–80% rate of mortality due to infection of P. aeruginosa in ventilator-associated pneumonia (Research has focused on type III secretion system (TTSS) secreting four exotoxins (ExoS, ExoT, ExoU and ExoY) [6]. ExoU is an effective virulence causing effector in TTSS. It is associated with morbidity and mortality in ventilator-associated pneumonia. Hogardt et al. reported that 40% of the isolates from such cases harbor the exoU gene [7].


3. Pathogenicity

The pathogenicity of P. aeruginosa makes its able to adhere and colonize in the presence of vast virulence factors and causing disease. Virulence factors used or synthesized by P. aeruginosa are enlisted in Table 1.

Virulence factor Action
  1. Colonization

Flagella Motility and invasion and adherence
Pili Adhesion; transfer of secretions
Exopolysaccharides Adherence and pathogen persistence
Lipopolysaccharide Endotoxin; inflammatory agent; adherence and biofilm formation
  1. Invasion

Alkaline protease Degrades immune system components
Elastase Degrade elastin; disrupt membranes; impair
Monocyte chemotaxis and degrade complement proteins
Lipase A and C Involvement in degradation
Phospholipase C Lung surfactant disruption
Protease Degrades complement factors, plasmin, IgG, and fibrinogen
Pyocyanin Inhibits lymphocyte proliferation; apoptosis of neutrophils
  1. Pathogenesis

Exotoxin A Unknown role—possibly causes apoptosis of cells
Biofilm Confers protection against biocides and immune system effectors as
Impenetrable to antibodies (Ab), antibiotics, and biocides
Hydrogen cyanide Unclear role, may be toxic agent.
Rhamnolipids Dissolve phospholipids
Type III secretion Exoenzyme (Exo) S, T and Y, and exotoxin U

Table 1.

Virulence factors produced and used by P. aeruginosa [8, 9, 10].


4. Biofilm

The pathogen colonized as planktonic form, and the cells convert to the sessile state to form biofilms. The hydrated structured matrices made up of exopolysaccharides and proteins, having ‘slimy’ characteristic can form on many surfaces from catheters to prokaryotic cells and eukaryotic. The main cause of persistent chronic infections is biofilm formation is essentially impenetrable inhabitants are protective for the bacterial strains from biocides [11]. The only one treatment to deal this situation is physical removal of the biofilm through surgery. Biofilms have heterogeneous populations of intra-species (phenotype and genotype, growth) and inter-species diversification. P. aeruginosa may be as dominant pathogen or with other pathogens such as Gram-negative Burkholderia cenocepacia and Gram-positive S. aureus [12]. The heterogeneous bacterial population of P. aeruginosa show distinct microenvironments for biofilms [13]. Metabolically active cells are at periphery and consume most of the oxygen, causing oxygen gradients in the biofilm [14]. The deeper layers of the biofilm have less metabolically active bacteria and are hypoxic. The actively growing peripheral bacterial cells of biofilms mostly susceptible to antibiotics or to the provided the drug which can penetrate slimy layer of the biofilm. Presence of a single polar flagellum made P. aeruginosa as motile. P. aeruginosa is exhibiting three distinctive types of motility and all of these types are required for development of biofilm which are;

  • Swimming: It is aided by the flagellum

  • Swarming: it requires both flagellum and type IV pili

  • Twitching: it depends upon type IV pili

[15, 16, 17, 18, 19, 20] (Figure 2).

Figure 2.

Different stages of the biofilm development. Modified from [21].


5. Flagella

The bacterial flagellum is protrudes from the cell body in the form a long, thin filament that consists of the basal body, the hook and the filament. The basal body is rooted in the cytoplasmic membrane having three rings the outer membrane lipopolysaccharide (L) ring, the peptidoglycan (P) ring and the cytoplasmic membrane supra-membrane (MS) ring. The hook is exposed to the surface and is a flexible universal joint between the filament and basal body. The filament is made of polymerized flagellin monomers (up to 20,000 subunits) capped by the flagellar cap, FliD, which acts as mucin adhesion [22, 23].

The initial attachment of the bacteria needs flagella and have involvement in maturation of biofilm. Klausen et al. reported that the initial microcolony formation is occurred by clonal growth and flagella are not involved in biofilm development in P. aeruginosa during attachment [24].


6. Pili and type I fimbriae

The type IV pili are best characterized, which are composed of the Pil A subunit in a form of a helical polymer. Hahn and Solow reported that these IV pili are localized to the poles of the bacterial cells and facilitate the adhesive properties of P. aeruginosa [25]. Type IV pili appear to be required for biofilm formation and host colonization. Cell aggregation and formation of microcolonies are promoted by Type IV pili [26, 27]. P. aeruginosa having three sets of type I fimbriae (CupA, CupB and CupC fimbriae) which assembled by the chaperone usher pathway. CupA fimbriae demonstrated as important for adherence to abiotic surfaces causing biofilm formation and auto-aggregation of small colony variants (SCV) in P. aeruginosa [28].


7. Exopolysaccharides

Major components of the biofilm matrix are the exopolysachcarides produced by the P. aeruginosa. These exopolysaccharides include Alginate, and Pel polysaccharide and Psl polysaccharide. The Pel and Psl are associated with the non-mucoid strain [29] and Alginate is associated with the mucoid strains [30].


8. Alginate

P. aeruginosa produces alginate (an exopolysaccharide). This is a capsular polysaccharide and is overproduced in mucoid strains of P. aeruginosa. It is a high molecular weight polymer composed of monomers of D-mannuronic acids and β-1, 4 linked L-guluronic which are not repeating. Mutations in the negative regulator MucA is mainly caused to isolate the alginate-producing variants from chronically infected CF lungs [31]. Bacteria prevent itself from phagocytosis by this polymer acts as a physical barrier and an adherence factor, it gets oxygen free radicals resulting in enhancement of resistance of the biofilm against the host immune defense and antimicrobial agents. The mucoid strains to remain persistent and establish chronic infections in the CF lung by the influence of alginate [32, 33]. Wozniak et al. has demonstrated that in non-mucoid P. aeruginosa strains (PAO1 and PA14) alginate is not the main component of the biofilm matrix [34].


9. Pel and Psl polysaccharides

The pel and psl operon are encoded polysaccharide associated in biofilm formation in PAO1, ZK2870 and PA14, the non-mucoid P. aeruginosa strains. The main components of the extracellular polysaccharide matrix are constituted by these polysaccharides [35].

The pel is an operon having 7 genes (PA3058 to PA3064), which encoding Pel polysaccharide biosynthetic proteins. The structure of Pel is unknown and it is a glucose-rich matrix polysaccharide and found to be involved in maintenance of biofilms and pellicle formation in P. aeruginosa PA14 strain. Sozzi and Smiley reported that biofilm formation is inversely regulated by cytoplasmic protein SadB1 result in altering the expression of Pel polysaccharide [36].

The psl, is an operon consist of 15 genes (PA2231 to PA2245), which encoding the Psl biosynthetic machinery. It is composed of a galactose-rich and mannose-rich polysaccharide. The exact structure of Psl has not been clarified yet. During attachment, Psl is holds and anchored bacteria during biofilm formation on the surface. Psl was associated in differentiation and maturation of P. aeruginosa biofilms in non-mucoid strains [37]. In P. aeruginosa psl and pel operons expresions are controlled by intracellular level of signaling molecule c-di-GMP (bis-(3′,5′)-cyclic-dimeric-guanosine monophosphate), the GacS/GacA/RsmZ and the Wsp chemosensory system [38, 39, 40].


10. Rhamnolipids

P. aeruginosa produce rhamnolipids, the biosurfactants. Enzymes of the rhlABC operon synthesized the rhamnolipids. Rhamnolipids are required for biofilm formation by promoting the formation of microcolony at the initial phase of the biofilm formation. These are associated with to maintain channels and void spaces in mature biofilms and also involved in biofilm dispersions [41, 42, 43].

11. Infections caused by P. aeruginosa

The ability of P. aeruginosa, to survive in indifferent environments including aquatic or marshes or even in low O2 or in very high temperatures (42°C) [44] resulting to withstand and survive on dry surfaces for more than 16 months by this pathogen [45]. It can colonize on dialysis machines, ‘in-dwelling’ appliances, sinks, floors, and toilet surfaces [46]. Immuno compromised host can be infected by P. aeruginosa by causing various clinical conditions, such as pneumonia, cystic fibrosis (CF), urinary tract infections, complications in clinical burns, and wounds [47, 48]. P. aeruginosa is a common isolate from the patients who are hospitalized for more than a week. It is associated with high rate of mortality within 24 hours, infection can results in pneumonia, septicemia and urinary tract infection.

In sever chronic infection especially in patients with cystic fibrosis (CF), P. aeruginosa is involved. The main cause of mortality is P. aeruginosa lung infection in CF patients [49]. Murray et al. reported transmissible epidemic strains of P. aeruginosa emerged within the CF community. In earlier reports, CF patients considered to having their own strain of P. aeruginosa from their environment not from other infected individuals [50]. It is known as the Liverpool epidemic strain (LES) in recent research of UK due to the most common isolate recovered from CF patients [51, 52]. P. aeruginosa has a major focus in research as it is reporting to transmitted from a CF patient to non-CF parents, and causing significant morbidity in infected patients. P. aeruginosa is considered an opportunistic pathogen and this is an unusual characteristic to infect healthy individuals. Manchester and Midlands 1, Clone C are considered as predominant epidemic strains of P. aeruginosa [53].

P. aeruginosa causes two types of respiratory infections. Acute (if patient have extended periods of ventilation) and chronic (if patient suffer from cystic fibrosis). Patients with these two types of infections in hospitalized settings are likely to be infected by this pathogen. Acute murine respiratory models used to identify a number of virulence factors in mutants of P. aeruginosa. The detailed studied is the TTSS proteins including ExoS, ExoT, ExoU and ExoY. Main contributor towards morbidity and mortality are ExoS, ExoT and ExoU as observed in a murein acute respiratory model (Table 2) [54].

Sr. no. Disease caused by P. aeruginosa
1 Respiratory tract infections (RTI)
2 Bacteremia; septicemia
3 Otitis externa
4 Skin infection; ecthyma gangrenosum, pyoderma, folliculitis, acne vulgaris
5 Eyes infections
6 Rare conditions like meningitis, perirectal infections and specific forms of osteomyelitis

Table 2.

Infectious diseases caused by P. aeruginosa [55].

The presence or absence of components of the TTSS can be correlated in human clinical results [55]. P. aeruginosa excreted a blue pigment Pyocyanin having antibacterial properties against other bacterial strains. The pyocyanin production also cause significant damage to lungs in murine acute respiratory infection, which demonstrated by an intranasal infection of adult CD-1 mice [49]. Quorum-sensing systems that are LasI, LasR [56], and RhlI [57] in P. aeruginosa contributing to acute infections. Intranasal infection in adult female Balb/c mice, and they also analyzed bacterial loads in lungs, liver and spleen after 16–18 hours of infection.

12. Cystic fibrosis

Cystic fibrosis trans-membrane conductance regulator (CFTR) mutation caused reduced chloride ion transport result in Cystic fibrosis (CF). It is a recessive genetic disorder. CF affected the development and functioning of various organs including immune system, pancreas and intestine, resulting a low life expectancy. The tissue damage is promoted in acute or chronic infections by constant stimulation of immune system effectors. In young CF patient P. aeruginosa is an important pathogen which lasts later stages. CF lung is an enriched with the oxygen gradients and nutrient. The oxygen gradients contribute the uniqueness in development of mucus layer and excessive consumption of the epithelial cells in CF lungs. P. aeruginosa is adaptable to many phenotypes in these types of conditions. A single isolate genome showed 68 mutations over the period of 90 months. The pathology in the lung in acute infections is due to the presence of elastase, flagella, LPS with O-side chains proteases, and pyocyanin.

P. aeruginosa contributed biofilms formation, produce rough LPS (no O-side chains), lack flagella, and overproduction of alginate during chronic infections. In chronic infections typically mucoid phenotype with lesser production of pyocyanin, pyoverdine, and elastase was observed. The antibiotic pressure causes P. aeruginosa to mutate from non-mucoid form to mucoid form. Small colony variants after a continued antibiotic exposure resulted in production of mannose-rich (psl) or glucose- (pel) polysaccharides. These are hyperpiliated, which are characterized as persistent to this specific phenotype. Liverpool epidemic strain (LES) reported as P. aeruginosa strains by over-production of pyocyanin.

The isolates of P. aeruginosa form CF changed their genome to get rid form acute virulence factors [56]. The loss of LasR function is one of the main genetic changes observed in P. aeruginosa isolates from CF patients. Many other acute infection models shown that because of deficiency in quorum-sensing, lasR mutants are less virulent than wild-type. Bacteria used this selective pressure of genetic change in genome to escape from host immune system in acute virulence in CF airways. An effective chronic CF isolate would be one, that isolate must lose its ability to be an effective acute infection isolate. lasR mutants have been examined for its advantages. The LasR mutants can grow on selected carbon and nitrogen sources as compared to wild-type.

13. Innate immune system

Immune system is acting as natural defense mechanism to prevent the invasion of pathogens. PRRs (Porcine reproductive and respiratory syndrome) stimulus received by nonspecific innate system and respond the innate effectors responses;

  • Phagocytosis by macrophages

  • cell death or

  • by the complement system with the membrane attack complex produced by the complement proteins or by natural killer (NK)

At the infection site the inflammatory response of effectors was induced by chemokines. Permanent tissue is damaged if continued stimulation of effectors by PAMPs (Pathogen associated molecular pattern) and virulence factors was induced [57].

14. Antibiotic resistance

P. aeruginosa is a free-living and aerobic bacillus that is isolated from soil and water in most of cases. Intrinsic resistance in P. aeruginosa causing high mortality due to a broad spectrum resistance of antibiotics and is able to quickly to acquire resistance genes by horizontal gene transfer. Fluoroquinolones, gentamicin and imipenem are restricted antibiotics as effective against P. aeruginosa and susceptibility to these antibiotics can vary between different strains. Bacterial infections are cured traditionally with the use of antibiotics and immune system is unable to have or eradicate this use of antibiotics.

Fluoroquinolones (ciprofloxacin) prevented DNA repair and replication [58]. Aminoglycosides, Beta-lactams (imipenam but not penicillins), 3rd and 4th generation cephalosporins, and fluoroquinolones are anti-pseudomonal drugs [59].

Colistin, is a drug having lesser side-effect profile, and mainly used against multi drug resistant strains (MDR) P. aeruginosa strains these days. The pattern or the use of antibiotic treatment now bettered towards the treatment of specific diseases including CF. The transmission of P. aeruginosa reduced by separation of infected and susceptible one and use of strict hygiene procedures [60].

The unavailability of the effective therapeutic option, the treatment of infections with pseudomonas is becoming difficult to deal a very few anti-pseudomonal drugs are being considered good for the treatment of emerging resistance strain, these include aminoglycosides beta-lactams, and fluoroquinolones [61, 62, 63].

The bactericidal MoA (mechanism of action) is significant for the survival by selection pressure for the fittest one. Antibiotic resistant bacteria are selected and propagated very well in the absence of the environmental resources competitions. Specific antibiotic resistance can be void of by the use of an alternative group of antibiotic. Bacteria have established active defense mechanisms which lead to MDR species such as methicillin-resistant Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Acinetobacter baumannii (A. baumannii), or P. aeruginosa are promoted as MDR strains and are difficult to eradicate this opportunistic pathogens [64].

15. P. aeruginosa and mechanisms of resistance

The mechanisms of resistance in P. aeruginosa against antibiotics can be intrinsic, adaptive, or acquired. Innately P. aeruginosa is resistant to many antibiotics. Intrinsically it has impermeable cell wall, outer membrane protein (Opr) channels, and multi-drug efflux pumps which give the bacteria resistance to certain antibiotics. Extended treatment and continuous use of higher therapeutic doses resulting in complete resistance [65].

16. Genomics of P. aeruginosa

The genome of a bacterium has two components first is the core genome and second the mobile genome. In a same species the core genome is common for all bacteria which include genes for the bacteria essential for development and the mobile genome can propagate within the whole genome [66, 67]. The mobile genome is varies between strains within a species. The mobile genome consists of a range of genetic elements such as insertion sequences, transposons, prophages, plasmids, and genomic islands. Horizontal gene transfer (HGT) processes such as conjugation, transformation, and transduction acquired the mobile genome. Genomic islands are the Clusters of genes in the mobile genome. Genomic islands encode gene products which enhance the fitness of a bacterium by survivability in new environment, increasing host range, and utilization of new nutrients. Genomic Island can be defined by various features [68].

In P. aeruginosa classical clades, the most of homologous exlB-exlA loci are existing in P. fluorescens, P. putida, and P. entomophila, signifying this locus acquired by horizontal transfer in Pseudomonas spp. Strain toxicity data related to neutrophils and macrophages and ability of inflammatory cells to phagocytic exlA+ strains are not accessible for recognition the behavior of these strains in vivo in detail. Different mechanism for expression are used by bacteria for virulence effect to infect mammals and plants and that ExlA is not required for bacterial plants toxicity. It shows unequal level of virulence that could not be aid in one toxin, Exl A [70]. All strains have lasB gene which have lasB PAO1 sequence at same location and with the sequence identity up to 91–98%. Quorum sensing is regulatory for the expression of LasB and lacking of Quorum sensing genes affected thelasB expression. Quorum sensing genes are lasR, lasI, vqsM, vqsR, rhlR, and rhlI all existed at same locations in genomes of all the strains of P. aeruginosa. The sequences displayed identity of 98%, except for the strain PA39 (92%). Internally a frameshift mutation of mvfR gene, coding for an important regulator of the Quorum sensing, observed in PA7 genome [71]. Same mutation is also present in mvfR genes and absent in most of strains hence lacking LasB activity.It is reported that in the absence of LasB activity lasB sequences and Quorum sensing cannot explained.

PAO1 Figure 3 (2001), PA14 (2005), PAS7 (2007) and LES (2008) are four complete sequenced genome available and P. aeruginosa is recent strain sequenced. Falagas et al. reported PAO1 had 44.2% of predicted ORFs in the class 4 with unknown function [72]. The labeling of pathogenicity islands in the genomic island must have virulence genes with known function other was this would be difficult to locate it (Figure 4).

Figure 3.

The novel hypervirulent ExlA-ExlB system [69].

Figure 4.

Circular representation of the P. aeruginosa genome.

P. aeruginosa PAO1 complete genome was available in 2001 and for remaining three strain genome sequences available in 2005–2008. The recent research data are based primarily on subtractive hybridization and microarray, for comparing the strains to reference strain that is PAO1 [73].

The differences in the genome targeted for further screening by using mutagenesis and virulence assays in models of in vivo infections. The current in vivo models commonly used for P. aeruginosa infection are:

  • The nematode worm Caenorhabditis elegans

  • The wax moth Galleria mellonella the plant Arabidopsis thaliana,

  • The fruit fly Drosophila melanogaster.

Murine used for infection models that imitate the human mood of infection are not common [74].

The results of current studies of pathogenicity island mutant have explained the effectiveness in finding their influence towards virulence. PAI I536–PAI V536 are five pathogenic island of E. coli and analyzed for their involvement in infection [75].

17. Quorum-sensing

Quorum-sensing systems controlled many virulent factors in P. aeruginosa such as the production of biofilm and the secretion of toxins [76]. Previously studies showed that insufficiency of the quorum-sensing systems can decrease the virulence in acute infection murine models. The use of insufficient quorum-sensing systems in a mutants murine burns injury model cause a decrease in mortality of the murine model. The ability of the bacteria to spread from the site of infection is also reduced. Lodise Jr. et al. reported the same results for a LasR mutant of PAO1 [77].

Quorum-sensing is a control system for coordination of gene expression in bacteria. As the level of an auto inducer goes to a threshold level, they caused the binding to specific bacterial receptors, in result gene transcription is initiated. In the result majority of the bacteria in a population expressing the same phenotype. P. aeruginosa is having two quorum-sensing systems, the Las system and the Rhl system.

18. Recent antibacterial agents against respiratory infections

18.1 Lactic acid bacteria

Food borne pathogenic and spoilage microorganisms are affected by the lactic acid bacteria (LAB) [78, 79], for example the growth of B. subtilis inhibited as it spoils bread [80]. Studies showed that Lactobacillus strains reported an inhibitory activity against E. coli [81]. Proteolytic activities and lipolytic activities of psychrophilic Pseudomonas causing food spoilage [82]. Lactobacillus species produced hydrogen peroxide which inhibits the growth of Pseudomonas species [42].

Lactic acid functions as the natural compound having antimicrobial activity and generally recognized as safe. Lactic acid has ability to inhibit the growth of Gram-negative species of Pseudomonadaceae and Enterobacteriaceae [83]. Lactic acid is used as a bio-preservative in fermented products.

Ribosome synthesized the bacteriocin extracellularly and secreted peptide complexes or bioactive peptides havingbacteriostatic orbactericidal effect [84]. Smart et al. reported Lactococcus lactis produced a bacteriocin called Nisin, which is studied in detailed, and applied as stabilizer to certain foods worldwide [85]. Bacteriocins are harmless due to quick proteolytic degradation by the gastrointestinal tract enzymes [86, 87].

Four major classes of bacteriocins are

  1. Lantibiotics: which are smaller and are heat stable peptides acting on membrane structures of the pathogens

  2. Non-lantibiotics: which are small are also heat stable peptides,

  3. Larger heat-labile proteins

  4. Complex bacteriocins [52, 88].

Most of bacteriocin are related to classes I and II. Proteinaceous compounds which are synthesized by ribosomes have bactericidal effect towards Gram-positive bacteria as compared to Gram-negative which have an additional layer composed of proteins, lipopolysaccharides and phospholipids [89, 90, 91].

Bacteriocins considered as potentially food-grade to increase food safety these can decrease the occurrence of foodborne diseases. These helped to lessen the use of chemical based preservatives and intensity of heat treatments for food preservations, resulting more naturally preserved food that is richer in nutritional and organoleptic properties [92].

Schillinger and Lucke has observed that the fact that most of bacteriocins have a narrower host range, which made them effective against closely related bacteria having same nutritive demands [93]. Lactic acid bacteria produced lactic acid functioning as a natural antimicrobial agent, having a generally known as safe to use. The growth of many Gram-negative species Pseudomonadaceae and Enterobacteriaceae was inhibited by the lactic acid bacteria. Forbio-preservation of the naturally fermented products lactic acid is used instead of other organic salts. Lactic acid is penetrates to cytoplasmic membrane of the organisms, which result in disruption of trans-membrane proton motive force and decrease in intracellular pH [94].

19. Antimicrobial property by hydrogen peroxide production

Bacterial enzymatic activity is destroyed by hydrogen peroxide which is a thermodynamically unstable and produced by Lactobacillus [95]. Other lactic-acid-producing bacteria and lactobacillus both are lacking heme and thus not utilizing the cytochrome systems for terminal oxidation. Flavoproteins are used by Lactobacilli, which convert oxygen to hydrogen peroxide and this mechanism, results in the formation of hydrogen peroxide in amounts which are degraded by the organism [96].

20. Antibacterial activity of nanoparticles (NPs)

The nanotechnology applications used in the food industry for food safety, disease treatment, for molecular and cellular biology as new tools, and for pathogen detection and protection [94]. NPs reported as applied in the nano tracer and nano-sensor fields in food industries [97, 98]. Nanotechnology used in food packaging to prevent contamination and to improve the shelf life of food [99, 100].

There are many types of NPs, and a variety of others are expected to introduce by the future researchers. Antibacterial agents are important and used in many industries, mainly in food industry. Cintas currently used antibacterial agents in the food industry are classified into two groups: inorganic agents and organic [101]. Inorganic antibacterial agents including NPs are used in food industry as they are stable under high pressures and temperatures conditions are required in food-processing, and regarded as safe to use for human and animals, as compared to organic materials [102, 103]. Studies showed that few NPs have selective toxicity to bacteria having lesser effects on human cells [104]. Foodborne outbreaks all over the world are increasing day by day and is important to control the causes. NPs are useful antibacterial agents that applied in the food industry. Silver (Ag) NPs are used in the medical and pharmaceutical industries. Ag NPs are very significant for the potential use in wide range of biological applications, as an antibacterial and antifungal agent for antibiotic resistant organisms to prevent infections. The concentration of NPs is linked with antibacterial activity. However, studies disagree with one another, indicating the mechanisms of NPs which causing antibacterial activity and toxicity to bacterial cells are very complex one [105, 106, 107]. Thus, it is challenging to classify the NPs as or adverse NPs or beneficial NPs towards bacteria. The tolerance property of bacteria having lesser growth rate is associated with the expression of genes related to stress-response [108].

After exposure to zinc oxide (ZnO) NP minimal inhibition concentration Staphylococcus aureus (S. aureus) and Salmonella typhimurium (S. typhimurium) were reduced to 0 within 4 and 8 h, respectively. Scanning electron micrographs of the targeted cell showed the completely lysis of the cells. Pseudomonas spp. were the most resistant and Bacillus cereus was the most sensitive among all of the studied strains against ZnO NPs.

Higher concentrations of Ag NPs showed the stronger antimicrobial activity. Ag NPs are used as antibacterial agents against Escherichia coli (E. coli) (Gram negative bacteria) [109].

The studied showed same results of Ag NPs between S. aureus, E. coli [110]. It was reported that smaller Ag NPs had effective antibacterial activity but having higher cytotoxicity. The antibacterial activity of Ag NPs is not only against the S. aureus and E. coli and, but also, P. aeruginosa [111]. ZnO NP inform of powders are widely used in coating electronic devices, cosmetics, catalysts and pigments. Instead of the extensive use of ZnO NPs, the safety of ZnO NPs for humans is not clear yet. In many studies the toxicity of metal oxide NPs and ZnO NPs towards mammalian cell and organs reported [112, 113]. Concentrations of ZnO less than 100 g/mL caused a substantial decrease of mitochondrial function decreased up to substantial level by concentration of ZnO (less than 100 g/mL). Weiss and Takhistov reported that Ag NPs decreased the cell viability of epithelial cells in lung [114]. For extracellular biosynthesis of gold nanoparticles P. aeruginosa used.

Moraru (2003) observed the AuNPs were prepared by reduction of gold ion in bacterial cell supernatant solutions [115]. Silver nanoparticles showed excellent antibacterial effect against pathogenic bacteria, Klebsiella pneumoniae and S. aureus [116, 117].

21. Conclusion

From the total P. aeruginosa isolates 66 to >90% were from the Lahore region and showed in vitro resistance to many of the commercially available antibiotics tested. Meropenem, Piperacillin, and Amoxicillin were the drugs for which there was the greatest susceptibility and represent recommended treatments for infections due to P. aeruginosa in our region. A significant killing of these resistant P. aeruginosa strains by factors present in supernates of Lactobacilli spp. was observed, suggesting that the use of Lactobacilli spp. as probiotics may be of value for the treatment or prevention of P. aeruginosa colonization. We also found strong in vitro anti-bacterial efficacy of Ag, Zn and Fe3 oxide NPS against the local P. aeruginosa isolates, suggestive of additional research into their practical application in a healthcare department [117]. The differences in pathogenicity due to between the P. aeruginosa isolates, which could be due to genes involved in the quorum sensing and biofilm formation which having the ability to develop infections. The research could be important in future studies as the already reported isolates used are have same environmental conditions which having the multidrug resistant P. aeruginosa strains. The genomic variations between the isolates of P. aeruginosa are also observed for detection of virulence genes in strains of P. aeruginosa could highlight the link between acute and chronic respiratory infections. The collected and provided data could conclude that the virulence genes are important in severity of acute and chronic respiratory infections in human beings.


  1. 1. Dasenbrook EC, Checkley W, Merlo CA, Konstan MW, Lechtzin N, Boyle MP. Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis. JAMA. 2010;303(23):2386-2392
  2. 2. Wong K, Roberts MC, Owens L, Fife M, Smith AL. Selective media for the quantitation of bacteria in cystic fibrosis sputum. J of medical microbiology. 1984;17(2):113-119
  3. 3. Gellatly SL, Hancock RE. P. aeruginosa: New insights into pathogenesis and host defenses. Pathogens and disease. 2013;67(3):159-173
  4. 4. Thrane S, Pedersen AM, Thomsen MBH, Kirkegaard T, Rasmussen BB, Duun-Henriksen AK, et al. A kinase inhibitor screen identifies Mcl-1 and Aurora kinase a as novel treatment targets in antiestrogen-resistant breast cancer cells. Oncogene. 2015;34(32):4199
  5. 5. Wolf P, Elsässer-Beile U. Pseudomonas exotoxin a: From virulence factor to anti-cancer agent. International J of Medical Microbiology. 2009;299(3):161-176
  6. 6. Chastre J, Fagon JY. Ventilator-associated pneumonia. American J of respiratory and critical care medicine. 2002;165(7):867-903
  7. 7. Hogardt M, Hoboth C, Schmoldt S, Henke C, Bader L, Heesemann J. Stage-specific adaptation of hypermutable P. aeruginosa isolates during chronic pulmonary infection in patients with cystic fibrosis. The J of infectious diseases. 2007;195(1):70-80
  8. 8. Jiang H, Jiang D, Shao J, Sun X. Magnetic molecularly imprinted polymer nanoparticles based electrochemical sensor for the measurement of gram-negative bacterial quorum signaling molecules (N-acyl-homoserine-lactones). Biosensors and Bioelectronics. 2016;75:411-419
  9. 9. Jimenez PN, Koch G, Thompson JA, Xavier KB, Cool RH, Quax WJ. The multiple signaling systems regulating virulence in P. aeruginosa. Microbiology and Molecular Biology Reviews. 2012;76(1):46-65
  10. 10. Lyczak JB, Cannon CL, Pier GB. Establishment of P. aeruginosa infection: Lessons from a versatile opportunist1. Microbes and Infection. 2000;2(9):1051-1060
  11. 11. Estela CRL, Alejandro PR. Biofilms: A survival and resistance mechanism of microorganisms. In: Antibiotic Resistant Bacteria-A Continuous Challenge in the New Millennium. Rijeka: InTech; 2012
  12. 12. Jageethadevi A, Saranraj P, Ramya N. Inhibitory effect of chemical preservatives and organic acids on the growth and organic acids on the growth of bacterial pathogens in poultry chicken. Asian J of Biochemical and Pharmaceutical Research. 2012;1(2):1-9
  13. 13. Ren S, Cai M, Shi Y, Xu W, Zhang XD. Influence of bronchial diameter change on the airflow dynamics based on a pressure-controlled ventilation system. International J for numerical methods in biomedical engineering. 2018;34(3):e2929
  14. 14. Kaye KS, Pogue JM. Infections caused by resistant gram-negative Bacteria: Epidemiology and management. Pharmacotherapy: The J of Human Pharmacology and Drug Therapy. 2015;35(10):949-962
  15. 15. Bradley JV. Nonrobustness in classical tests on means and variances: A large-scale sampling study. Bulletin of the Psychonomic Society. 1980;15(4):275-278
  16. 16. Whitchurch CB, Hobbs M, Livingsston SP, Krishnapillai V, Mattick JS. Characterisation of a P. aeruginosa twitching motility gene and evidence for a specialised protein export system widespread in eubacteria. Gene. 1991;101(1):33-44
  17. 17. Darzins A. Characterization of a P. aeruginosa gene cluster involved in pilus biosynthesis and twitching motility: Sequence similarity to the chemotaxis proteins of enterics and the gliding bacterium Myxococcus xanthus. Molecular Microbiology. 1994;11(1):137-153
  18. 18. Feldman GJ, Cousins RD. Unified approach to the classical statistical analysis of small signals. Physical review D. 1998;57(7):3873
  19. 19. Kohler KJ. Investigating unscripted speech: Implications for phonetics and phonology. Phonetica. 2000;57(2-4):85-94
  20. 20. Rashid MH, Kornberg A. Inorganic polyphosphate is needed for swimming, swarming, and twitching motilities of P. aeruginosa. Proceedings of the National Academy of Sciences. 2000;97(9):4885-4890
  21. 21. McDougald LR. Histomoniasis (Blackhead) and other protozoan diseases of the intestinal tract. In: Saif YM, Fadly AM, Glisson JR, LR MD, Nolan LK, et al., editors. Diseases of Poultry. Ames: Blackwell Academic Publishing Professional; 2008, 2008. pp. 1095-1105
  22. 22. Arora S, Lund C, Motwani R, Sudan M, Szegedy M. Proof verification and the hardness of approximation problems. J of the ACM (JACM). 1998;45(3):501-555
  23. 23. Chevance FF, Hughes KT. Coordinating assembly of a bacterial macromolecular machine. Nature reviews microbiology. 2008;6(6):455
  24. 24. Klausen M, Aaes-Jørgensen A, Molin S, Tolker-Nielsen T. Involvement of bacterial migration in the development of complex multicellular structures in P. aeruginosa biofilms. Molecular Microbiology. 2003;50(1):61-68
  25. 25. Hahn F, Solow RM. A Critical Essay on Modern Macroeconomic Theory. USA: MIT Press, AWS; 1997
  26. 26. Khalil R, Gomaa M. Evaluation of the microbiological quality of conventional and organic leafy greens at the time of purchase from retail markets in Alexandria, Egypt. Polish Journal of Microbiology. 2014;63:237-243
  27. 27. Vallet-Regi M, Ramila A, Del Real RP, Pérez-Pariente J. A new property of MCM-41: Drug delivery system. Chemistry of Materials. 2001;13(2):308-311
  28. 28. Lewis K. Riddle of biofilm resistance. Antimicrobial Agents and Chemotherapy. 2001;45(4):999-1007
  29. 29. Friedman L, Kolter R. Two genetic loci produce distinct carbohydrate-rich structural components of the P. aeruginosa biofilm matrix. J of bacteriology. 2004;186(14):4457-4465
  30. 30. Govan JR, Deretic V. Microbial pathogenesis in cystic fibrosis: Mucoid P. aeruginosa and Burkholderia cepacia. Microbiological Reviews. 1996;60(3):539-574
  31. 31. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. New England J of Medicine. 2011;365(18):1663-1672
  32. 32. Krieg M, Aramendia PF, Braslavsky SE, Schaffner K. 124-kDa Phytochrome in model membrane systems: Studies of the ii700 intermediates with the protein covalently bound to preformed liposomes. Photochemistry and Photobiology. 1988;47(2):305-310
  33. 33. Worlitzsch D, Tarran R, Ulrich M, Schwab U, Cekici A, Meyer KC, et al. Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. The J of clinical investigation. 2002;109(3):317-325
  34. 34. Wozniak MA, Desai R, Solski PA, Der CJ, Keely PJ. ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix. The Journal of Cell Biology. 2003;163(3):583-595
  35. 35. Matsuo Y, Ishizuka M. Keyword extraction from a single document using word co-occurrence statistical information. International J on Artificial Intelligence Tools. 2004;13(01):157-169
  36. 36. Sozzi T, Smiley MB. Antibiotic resistances of yogurt starter cultures Streptococcus thermophilus and Lactobacillus bulgaricus. Applied Environmental Microbiology. 1980;40:862-865
  37. 37. Caiazza NC, Merritt JH, Brothers KM, O’Toole GA. Inverse regulation of biofilm formation and swarming motility by P.aeruginosa PA14. J of bacteriology. 2007;189(9):3603-3612
  38. 38. Sadikot RT, Blackwell TS, Christman JW, Prince AS. Pathogen–host interactions in P. aeruginosa pneumonia. American J of respiratory and critical care medicine. 2005;171(11):1209-1223
  39. 39. Rickard AH, Gilbert P, High NJ, Kolenbrander PE, Handley PS. Bacterial coaggregation: An integral process in the development of multi-species biofilms. Trends in Microbiology. 2003;11(2):94-100
  40. 40. Hickman JW, Tifrea DF, Harwood CS. A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(40):14422-14427
  41. 41. Ventre I, Goodman AL, Vallet-Gely I, Vasseur P, Soscia C, Molin S, et al. Multiple sensors control reciprocal expression of P. aeruginosa regulatory RNA and virulence genes. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(1):171-176
  42. 42. Lee H, Dellatore SM, Miller WM, Messersmith PB. Mussel-inspired surface chemistry for multifunctional coatings. Science. 2007;318(5849):426-430
  43. 43. Davey Smith G, Ebrahim S. ‘Mendelian randomization’: Can genetic epidemiology contribute to understanding environmental determinants of disease? International J of epidemiology. 2003;32(1):1-22
  44. 44. Boles BR, Thoendel M, Singh PK. Rhamnolipids mediate detachment of P. aeruginosa from biofilms. Molecular Microbiology. 2005;57(5):1210-1223
  45. 45. Pamp SJ, Tolker-Nielsen T. Multiple roles of biosurfactants in structural biofilm development by P. aeruginosa. J of bacteriology. 2007;189(6):2531-2539
  46. 46. Bjarnsholt T, Givskov M. Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens. Philosophical Transactions of the Royal Society B: Biological Sciences. 2007;362(1483):1213-1222
  47. 47. Kramer A, Schwebke I, Kampf G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC infectious diseases. 2006;6(1):130
  48. 48. De Kievit TR, Gillis R, Marx S, Brown C, Iglewski BH. Quorum-sensing genes in P. aeruginosa biofilms: Their role and expression patterns. Applied and Environmental Microbiology. 2001;67(4):1865-1873
  49. 49. Mesaros N, Nordmann P, Plésiat P, Roussel-Delvallez M, Van Eldere J, Glupczynski Y, et al. P. aeruginosa: Resistance and therapeutic options at the turn of the new millennium. Clinical Microbiology and Infection. 2007;13(6):560-578
  50. 50. Murray TS, Egan M, Kazmierczak BI. P. aeruginosa chronic colonization in cystic fibrosis patients. Current Opinion in Pediatrics. 2007;19(1):83-88
  51. 51. Scott FW, Pitt TL. Identification and characterization of transmissible P. aeruginosa strains in cystic fibrosis patients in England and Wales. J of medical microbiology. 2004;53(7):609-615
  52. 52. Salunkhe P, Smart CH, Morgan JAW, Panagea S, Walshaw MJ, Hart CA, et al. A cystic fibrosis epidemic strain of P. aeruginosa displays enhanced virulence and antimicrobial resistance. J of bacteriology. 2005;187(14):4908-4920
  53. 53. Shorr AF, Tabak YP, Gupta V, Johannes RS, Liu LZ, Kollef MH. Morbidity and cost burden of methicillin-resistant Staphylococcus aureus in early onset ventilator-associated pneumonia. Critical care. 2006;10(3):R97
  54. 54. McCallum AK. Mallet: A Machine Learning for Language Toolkit. USA: AWS; 2002
  55. 55. Shaver CM, Hauser AR. Relative contributions of P. aeruginosa ExoU, ExoS, and ExoT to virulence in the lung. Infection and Immunity. 2004;72(12):6969-6977
  56. 56. Hauser MD, Chomsky N, Fitch WT. The faculty of language: What is it, who has it, and how did it evolve? Science. 2002;298(5598):1569-1579
  57. 57. Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. New England J of Medicine. 2005;352(26):2682-2695
  58. 58. Pearson SF. Behavioral asymmetries in a moving hybrid zone. Behavioral Ecology. 2000;11(1):84-92
  59. 59. Allewelt M, Coleman FT, Grout M, Priebe GP, Pier GB. Acquisition of expression of the P. aeruginosa ExoU cytotoxin leads to increased bacterial virulence in a murine model of acute pneumonia and systemic spread. Infection and Immunity. 2000;68(7):3998-4004
  60. 60. Laskowski MA, Kazmierczak BI. Mutational analysis of RetS, an unusual sensor kinase-response regulator hybrid required for P. aeruginosa virulence. Infection and Immunity. 2006;74(8):4462-4473
  61. 61. Siddique S, Shah ZH, Shahid S, Yasmin F. Prepara-tion, characterization and antibacterial activity of ZnO nanoparticles on broad spectrum of microorganisms. Acta Chimica Slovenica. 2013;60:660-665
  62. 62. Smith SC, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: Endorsed by the National Heart, Lung, and Blood Institute. J of the American College of Cardiology. 2006;47(10):2130-2139
  63. 63. D’argenio DA, Wu M, Hoffman LR, Kulasekara HD, Déziel E, Smith EE, et al. Growth phenotypes of P. aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients. Molecular Microbiology. 2007;64(2):512-533
  64. 64. Tang P, Hung MC, Klostergaard J. Length of the linking domain of human pro-tumor necrosis factor determines the cleavage processing. Biochemistry. 1996;35(25):8226-8233
  65. 65. Rumbaugh KP, Griswold JA, Iglewski BH, Hamood AN. Contribution of quorum sensing to the virulence of P. aeruginosa in burn wound infections. Infection and Immunity. 1999;67(11):5854-5862
  66. 66. Christensen JH, Christensen OB. A summary of the PRUDENCE model projections of changes in European climate by the end of this century. Climatic Change. 2007;81(1):7-30
  67. 67. Nowroozi J, Mirzaii M, Norouzi M. Study of Lactobacillus as probiotic bacteria. Iranian J of Public Health. 2004;33:1-7
  68. 68. Lau SK, Woo PC, Fung AM, Chan KM, Woo GK, Yuen KY. Anaerobic, non-sporulating, gram-positive bacilli bacteraemia characterized by 16S rRNA gene sequencing. J of medical microbiology. 2004;53(12):1247-1253
  69. 69. Sonnleitner E, Haas D. Small RNAs as regulators of primary and secondary metabolism in Pseudomonas species. Applied Microbiology and Biotechnology. 2011;91(1):63-79
  70. 70. Mikkelsen H, Sivaneson M, Filloux A. Key two-component regulatory systems that control biofilm formation in P. aeruginosa. Environmental Microbiology. 2011;13(7):1666-1681
  71. 71. Breidenstein EB, de la Fuente-Núñez C, Hancock RE. P. aeruginosa: All roads lead to resistance. Trends in Microbiology. 2011;19(8):419-426
  72. 72. Falagas ME, Kasiakou SK, Saravolatz LD. Colistin: The revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clinical Infectious Diseases. 2005;40(9):1333-1341
  73. 73. Arancibia F, Bauer TT, Ewig S, Mensa J, Gonzalez J, Niederman MS, et al. Community-acquired pneumonia due to gram-negative bacteria and P. aeruginosa: Incidence, risk, and prognosis. Archives of Internal Medicine. 2002;162(16):1849-1858
  74. 74. Mah TFC, O’toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends in Microbiology. 2001;9(1):34-39
  75. 75. Moore NM, Flaws ML. Epidemiology and pathogenesis of P. aeruginosa infections. Clinical laboratory science. 2011;24(1):43
  76. 76. Alekshun MN, Levy SB. Molecular mechanisms of antibacterial multidrug resistance. Cell. 2007;128(6):1037-1050
  77. 77. Lodise TP Jr, Lomaestro B, Drusano GL. Piperacillin-tazobactam for P. aeruginosa infection: Clinical implications of an extended-infusion dosing strategy. Clinical Infectious Diseases. 2007;44(3):357-363
  78. 78. Hart CA, Winstanley C. Persistent and aggressive bacteria in the lungs of cystic fibrosis children. British Medical Bulletin. 2002;61(1):81-96
  79. 79. Ou HH, Lo SL. Review of titania nanotubes synthesized via the hydrothermal treatment: Fabrication, modification, and application. Separation and Purification Technology. 2007;58(1):179-191
  80. 80. Winstanley C, Langille MG, Fothergill JL, Kukavica-Ibrulj I, Paradis-Bleau C, Sanschagrin F, et al. Newly introduced genomic prophage islands are critical determinants of in vivo competitiveness in the liverpool epidemic strain of P. aeruginosa. Genome Research. 2009;19(1):12-23
  81. 81. Hilker M, Fatouros NE. Plant responses to insect egg deposition. Annual Review of Entomology. 2015;60:493-515
  82. 82. Roy A, Kucukural A, Zhang Y. I-TASSER: A unified platform for automated protein structure and function prediction. Nature protocols. 2010;5(4):725
  83. 83. Stover CK, Pham XQ , Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, et al. Complete genome sequence of P. aeruginosa PAO1, an opportunistic pathogen. Nature. 2000;406(6799):959
  84. 84. Choi CW, Vanhatalo A, Ahvenjärvi S, Huhtanen P. Effects of several protein supplements on flow of soluble non-ammonia nitrogen from the forestomach and milk production in dairy cows. Animal Feed Science and Technology. 2002;102(1-4):15-33
  85. 85. Smart SK, Cassady AI, Lu GQ , Martin DJ. The biocompatibility of carbon nanotubes. Carbon. 2006;44(6):1034-1047
  86. 86. Mahajan-Miklos S, Tan MW, Rahme LG, Ausubel FM. Molecular mechanisms of bacterial virulence elucidated using a P. aeruginosaCaenorhabditis elegans pathogenesis model. Cell. 1999;96(1):47-56
  87. 87. Rahme LG, Ausubel FM, Cao H, Drenkard E, Goumnerov BC, Lau GW, et al. Plants and animals share functionally common bacterial virulence factors. Proceedings of the National Academy of Sciences. 2000;97(16):8815-8821
  88. 88. Duan K, Surette MG. Environmental regulation of P. aeruginosa PAO1 Las and Rhl quorum-sensing systems. J of bacteriology. 2007;189(13):4827-4836
  89. 89. Tan H, Feng Y, Chen J, Tang M, Li C, Xu L, et al. Preparation and characterization of Nano-ZnO antibacterial cardboard. Nanoscience and Nanotechnology Letters. 2017;9(3):241-246
  90. 90. Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: Antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126(6):1620-1633
  91. 91. Schillinger U, Lücke FK. Antibacterial activity of Lactobacillus sake isolated from meat. Applied and Environmental Microbiology. 1989;55(8):1901-1906
  92. 92. Sawai J. Quantitative evaluation of antibacterial activities of metallic oxide powders (ZnO, MgO and CaO) by conductimetric assay. J of microbiological methods. 2003;54(2):177-182
  93. 93. Vogel P, Beacom JF. Angular distribution of neutron inverse beta decay, ν̄ e+ p→ e++. Physical review D. 1999;60(5):053003
  94. 94. Urga G. The Econometrics of Panel Data: A Selective Introduction (No. 99151). UK: EconPapers; 1992
  95. 95. Rodríguez LF, Reipurth B. Detection of radio continuum emission from the Herbig-Haro objects 80 and 81 and their suspected energy source. Revista Mexicana de Astronomia y Astrofisica. 1989;17:59-63
  96. 96. Ünlütürk A, Turantaş F. Gıda Mikrobiyolojisi. İzmir: Mengi Tan Basımevi; 1998
  97. 97. Daeschel MA. Antimicrobial substances from lactic acid bacteria for use as food preservatives. J of FoodPreservatives. 2011;44:164-167
  98. 98. DOORE S. Organic acids. In: Antimicrobials in foods. Aspen, NY. 1993. p. 95
  99. 99. Garneau S, Martin NI, Vederas JC. Two-peptide bacteriocins produced by lactic acid bacteria. Biochimie. 2002;84(5-6):577-592
  100. 100. Dalié DKD, Deschamps AM, Richard-Forget F. Lactic acid bacteria–potential for control of mould growth and mycotoxins: A review. Food Control. 2010;21(4):370-380
  101. 101. Cintas P. Synthetic organoindium chemistry: What makes indium so appealing? Synlett. 1995;1995(11):1087-1096
  102. 102. De Vuyst L, Vandamme EJ. Antimicrobial potential of lactic acid bacteria. In: Bacteriocins of lactic acid bacteria. Boston, MA: Springer; 1994. pp. 91-142
  103. 103. Klaenhammer TR. Bacteriocins of lactic acid bacteria. Biochimie. 1988;70(3):337-349
  104. 104. González-Martínez BE, Gómez-Treviño M, Jiménez-Salas Z. Bacteriocinas de probióticos. Revista Salud Pública y Nutrición. 2003;4(2):64-70
  105. 105. Deegan LH, Cotter PD, Hill C, Ross P. Bacteriocins: Biological tools for bio-preservation and shelf-life extension. International dairy J. 2006;16(9):1058-1071
  106. 106. Abee T, Krockel L, Hill C. Bacteriocins: Modes of action and potentials in food preservation and control of food poisoning. Inter J of food Microb. 1995;28(2):169-185
  107. 107. Dortu C, Thonart P. Bacteriocins from lactic acid bacteria: Interest for food products biopreservation. Biotechnologie, Agronomie, Société et Environnement. 2009;13(1):143-154
  108. 108. Bromberg L, Temchenko M, Alakhov V, Hatton TA. Bioadhesive properties and rheology of polyether-modified poly (acrylic acid) hydrogels. International Journal of Pharmaceutics. 2004;282(1-2):45-60
  109. 109. Gálvez A, Abriouel H, López RL, Omar NB. Bacteriocin-based strategies for food biopreservation. International J of food microbiology. 2007;120(1-2):51-70
  110. 110. Davoodabadi A, Dallal MMS, Foroushani AR, Douraghi M, Harati FA. Antibacterial activity of Lactobacillus spp. isolated from the feces of healthy infants against enteropathogenic bacteria. Anaerobe. 2015;34:53-58
  111. 111. Rangasamy S, Tak YK, Kim S, Paul A, Song JM. Bifunctional therapeutic high-valence silver-pyridoxine nanoparticles with proliferative and antibacterial wound-healing activities. J of biomedical nanotechnology. 2016;12(1):182-196
  112. 112. Collins EB, Aramaki K. Production of hydrogen peroxide by Lactobacillus acidophilus. J of dairy science. 1980;63(3):353-357
  113. 113. Dahiya RS, Speck ML. Hydrogen peroxide formation by lactobacilli and its effect on Staphylococcus aureus. J of Dairy Science. 1968;51(10):1568-1572
  114. 114. Weiss J, Takhistov P. J Mc Clements. Functional materials in food nanotechnology. Journal of Food Science. 2006;71(9):R107-R116
  115. 115. Moraru CI, Panchapakesan CP, Huang Q , Takhistov P, Liu S, Kokini JL. Nanotechnology: A new frontier in food science. Food Technology. 2003;57(12):24-29
  116. 116. Jin T, Sun D, Su JY, Zhang H, Sue HJ. Antimicrobial efficacy of zinc oxide quantum dots against Listeria monocytogenes, Salmonella enteritidis, and Escherichia coli O157: H7. J of food science. 2009;74(1):46-52
  117. 117. Rehman S, Ali NM, Pier BG, Liaqat I. In vitro susceptibility of P. aeruginosa isolated from acute and chronic pulmonary infection to antibiotics, Lactobacillus competition and metal nanoparticles. PJZ. 2018;50(6)

Written By

Nazish Mazhar Ali, Safia Rehman, Syed Abdullah Mazhar, Iram Liaqat and Bushra Mazhar

Submitted: September 6th, 2019 Reviewed: July 29th, 2020 Published: December 9th, 2020