Open access peer-reviewed chapter

Approaches to Enhance Therapeutic Activity of Drugs against Bacterial Biofilms

Written By

Sankar Veintramuthu and Selliamman Ravi Mahipriya

Submitted: 23 January 2022 Reviewed: 11 March 2022 Published: 30 April 2022

DOI: 10.5772/intechopen.104470

From the Edited Volume

Focus on Bacterial Biofilms

Edited by Theerthankar Das

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Biofilm may be a consortium of microbial species where the cells of microbes attach to both life form and inanimate surfaces inside a self-made matrix of extracellular polymeric substance (EPS). Biofilm matrix surrounding the polymicrobial environment makes them highly resistant to harsh conditions and antibacterial treatments. The two significant factors that differentiate planktonic from biofilm resident microbes are EPS containing a variety of macromolecules and a diffusible molecule for transferring signals known as quorum sensing (QS). Against this backdrop of microbial resistance and cell signaling, different approaches have been developed to interfere with the specific mechanisms of intracellular and extracellular targets that include herbal active compounds and synthetic nanoparticles. This chapter outlines the features of biofilm development and the approaches with the evidence that can be incorporated into clinical usage.


  • biofilm
  • antimicrobial resistance
  • quorum sensing
  • herbal compounds
  • nanoparticles

1. Introduction

In seventeenth century, Antonie von Leeuwenhoek saw microbial aggregates on the scrapings of the plaque from his teeth that was termed as “biofilm” by Bill Costerton in 1978 [1]. The biofilms were not characterized for their physical and chemical properties until the end of 1960 [2]. The evolution of scanning electron microscopy and transmission electron microscopy allowed for identifying the biofilm from wastewater treatment plant [3] after when Heukelekian and Heller identified the “Bottle effect” on marine microbes where there is a significant difference in the microbial population between in situ and in vitro due to environmental or man-made changes. Biofilm is an aggregation of microbially derived sessile communities having various bacterial colonies or individual cells in the group, which adheres to the surface. This group of cells attaches on an extracellular polymeric substance (EPS), a matrix that is mostly comprised of environmental DNA (eDNA), proteins, and polysaccharides, which provides significantly excessive resistance to antibiotics [4]. Bacterial biofilm can be formed in response to various factors such as high salt concentration, restricted nutrients, high pH and pressure, and UV radiation. Biofilm life process is depicted in Figure 1.

Figure 1.

Biofilm life process. (1) Planktonic bacteria attaches to the exterior face. (2) Adhesion, irreversible attachment occurs at this phase. (3) EPS is secreted and results in a matrix that forms the basis for biofilm’s structure and initiates the onset of biofilm maturation. (4) The biofilm becomes completely matured, with the tower-like structures dispersed with water channels for the movement of oxygen, nutrients, and for discharging waste products.

The biofilm formation can be described in three steps:

  1. Flexible attachment of bacteria to the surface subsequently irreversible attachment with the help of adhesive structures of bacteria.

  2. Production of EPS and development of an organized structure entrapped inside an EPS matrix.

  3. Finally, bacterial cell starts to break out from the biofilm and spread into the habitat through chemical signaling [5].


2. Biofilm: a threat to antibiotics and infections caused by biofilm

Around 80% of chronic and periodic microbial infections in the human bodies are caused by bacterial biofilm. Bacteria’s present inside the biofilm aids to the chronic phase of infection, when released from the biofilm can cause an acute phase of infection [6]. The infections caused by bacterial biofilm can be placed in two broad categories such as device and non-device-associated infections. They can develop on or inside medical devices that are built in body such as central venous catheters, mechanical heart valves, pacemakers, urinary catheters, which cover both Gram-positive and Gram-negative bacteria or yeasts. These organisms on the medical devices may cause blood stream and urinary tract infections in the patient [7]. Table 1 shows the microbial species that colonizes the devices based on the type of medical device and time taken for their action.

S. NoMedical deviceMicrobial organisms
1.Contact lensesEscherichia coli, Staphylococcus epidermidis, Pseudomonas. aeruginosa, species of Candida, Serratia and Proteus, Staphylococcus aureus. [8]
2.Central venous cathetersKlebsiella species, P. aeruginosa, and Enterobacter species [9]
3.Mechanical heart valveEnterococcus and Candida spp, Streptococcus species, S. aureus, S. epidermidis, Bacillus [10]
4.Urinary cathetersE. coli, Enterococcus faecalis, S. epidermidis, P. aeruginosa, Proteus mirabilis, Klebsiella pneumonia [11]

Table 1.

Medical devices and associated biofilm organisms.

Microbial biofilm show 10–1000 times more antibiotic resistance than the planktonic species [12]. Bacterial biofilm offers huge evolutionary advantage for the bacteria including changes in environmental pH, resistance to antimicrobial agents, and phagocytic attack [13].


3. Quorum sensing (QS) and interaction

The bacterial cells have intercellular communication that is delivered through the extracellular signaling molecules known as autoinducers. The collection of signaling molecules enables individual bacterial cells to analyze the total number of bacteria, that is, cell density known as quorum sensing. In low-density planktonic populations, bacteria releases low-molecular-weight, highly diffusible, signal molecules (autoinducers, such as oligopeptides in Gram-positive bacteria and N-acyl-L-homoserine lactones in Gram-negative bacteria) at very low levels to produce changes in gene expression. When critical mass of bacterial population becomes high, the concentration of autoinducer molecules increases in the EPS followed by allowing individual bacteria to sense the presence of other bacterial species [14].


4. Conventional treatments and antimicrobial resistance

Biofilms are considered to be important owing to their potency in showing resistance toward antibiotics and antifungals. Once routed within the wound infection, biofilm shows enhanced tolerance to conventional treatments. Antibiotics work by deranging the cell wall of bacteria and affecting the DNA replication, repair, and protein synthesis. Apparently biofilm has various mechanisms through which they resist the effectiveness of antibiotics [15]. The primary defense mechanism involves EPS, which is capable of restricting the permeability of antibiotics into the cell thereby trapping them in the pores, followed by acidic internal environment and lack of oxygen. Ultimately, the lysis of genetic component can be carried between the cells to extend antimicrobial resistance.

The persister cells within the biofilm have the potency to restrict the effects of antibiotics targeting the cell division [16]. Figure 2 illustrates the mechanism through which biofilm develops resistance to conventional antibiotics [17].

Figure 2.

Antibiotic resistance associated with biofilm.

The resistance can be developed through persistent cells, phenotype of the biofilm, inhibition in antibiotics penetration, production of enzymes that resist the action of antimicrobial agents.


5. Nanoparticles (NPs) as antibiofilm agents

Nanotechnology is fascinating, which likely benefited the field of biomedical and became widely conceded for the treatment of various diseases. Numerous resistance mechanisms set biofilm as one of the major disputes in infection treatment, which can be addressed by the strategy of using nanoparticles. NPs have two or three dimensions in the size range of 1 to 100 nm. They are of various types based on their size, shape, and composition [18]. Their higher surface area built them as suitable drug career, which has the capability to immobilize the compounds on their surface to increase their solubility and targeted delivery [19]. They can be of two types, polymer NPs and metallic NPs. Polymer NPs also possess the advantage of retaining the drug inside the cavity and delivers the drug at the target area in either entangled or immobilized form. Reports suggest that NPs disrupt the integrity of biofilm by interacting with EPS, eDNA, proteins, lipids, and biofilm release reactive oxygen species (ROS) on interaction with NPs that can damage the cell envelope, cell membranes, cell structures, and biomolecules of the microbes. Figure 3 represents the general mechanism involved in combating biofilm through NPs [20].

Figure 3.

Depiction of various mechanisms involved in combating biofilm through NPs.

The nanoparticles can restrict biofilm by disruption electron transport between cell membrane, damaging the peptidoglycan layer, breaking through the cell membrane, denaturation of proteins, and DNA damage.


6. Synthesis of nanoparticles

Nanoparticles can be synthesized in laboratory broadly using two different approaches, that is, bottom-up and top-down techniques. The top-down approach implies breaking the bulk material into nanosized structures, which is based on miniaturizing the bulk substance through fabrication process and produces the NPs of appropriate properties. Bottom-up technique is an alternative approach because it creates less waste and involves building up of a material from the bottom [21].


7. Types of nanoparticles

Polymeric NPs can be engineered to release antibiotics, antibacterial agents, and bacteriostatic peptides or by modifying their chemical surface. The antibacterial activity of these organic NPs is due to polycationic groups accountable for cell damage through ion exchange interaction between bacteria and polymer surface with charges [22]. Metals are used in the synthesis of nanoparticles because of their antibacterial property broadly used in managing infections. Metallic nanoparticles can exert physical disruption to bacterial biofilms. Table 2 enlists the types of metallic nanoparticles and their potential antimicrobial property [23].

S. NoMetallic nanoparticlesProperties
1.Zinc oxideThese NPs gets accumulated inside the cell releasing H2O2 and zinc ions thereby causing cell wall disruption.
2.Titanium dioxideGeneration of reactive oxygen species.
3.Copper oxideLipid oxidation takes place through reactive oxygen species and hydroxyl free radicals.
4.Carbon nanotubeReactive oxygen species results in cell wall disruptionthereby oxidizing lipids and proteins.
5.GoldThey produce strong electrostatic effects and reacts with cell membrane.
6.SilverReleases silver ions and causes electron impairment DNA damage.

Table 2.

Metallic nanoparticles and their antimicrobial property.

The pH of micro-environment, magnetic field, or light can be used to turn on the nanomaterials or transform it to more active species enhancing their antibiofilm activity. These are often metallic nanoparticles due to their broad-spectrum antimicrobial activity and rich surface chemistry [24]. For negatively charged bacteria, the adhesion property rises because of the positively charged surface of NPs and the binding takes place through electrostatic interactions and Van der Waals interaction especially to cell membrane proteins [25].


8. Metal NPs against biofilm

CuO NPs inhibit formation of biofilm that was studied by Agarwal et al. that concluded eradication of biofilm formed by MRSA and E. coli with the exposure period of 4 days to CuO NPs at the concentration of 50 μg/ml [26]. ZnO NPs can exhibit antibacterial action between the concentration of 20–500 μg/ml for E. coli and S. aureus that can be enhanced by additional physical exposure and amplified by ultrasound [27]. MgO NPs can act against Gram-positive and Gram-negative bacteria, bacterial spores, and viruses at higher concentration of 100–1200 μg/ml. TiO2 NPs can destroy biofilms of both Gram-positive and Gram-negative bacteria but the latter being more sensitive due to the sturdy layer of peptidoglycan that increases the absorption of reactive radicals [28]. However, their toxicity to humans and environment outweighs their advantages. Gold and silver NPs offer huge advantages such as higher surface area to volume ratio, small size, amenability, cheaper method of synthesis. Extensive research studies have been accomplished over the recent areas involving AgNPs and AuNPs. Three important steps involved in their antimicrobial action are a) interaction with biofilm when it comes into contact with the surface, b) subsequent penetration of NPs into the cell based on this interaction, and c) NPs as a whole or ions (Au+ and Ag+) reacts with cellular and biofilm components. The factor that plays significant role in penetration includes particle size, surface chemistry, surface charge, and concentration.

8.1 Silver nanoparticles: a biofilm buster

Silver has been used since remote time because of their therapeutic properties and their antibacterial activity and also explored through extensive research in medical field. Topical ointments and creams contain silver for treating burn wound infection. Several approaches are involved in synthesis of AgNPs, which include the use of microorganisms and plants but one of the easiest and convenient methods is through chemical synthesis [29]. Table 3 enlists some of the sources that can be used for the synthesis of AgNP.

S.NoApproachesSources for synthesis
1.Microbial approachCedecea sp., Pseudomonas sp., Lactobacillus plantarum, Aspergillus fumigatus, Aeromonas sp., Klebsiella pneumonia, Corynbacterium sp., Enterobacter cloacae, Verticillium sp., Fusarium semitectum, Fusarium oxysporium. [30, 31, 32]
2.Plant synthesisAloe vera leaf extract, Azadirachta indica, Cinnamomum camphora, Emblica officinalis, Pinus eldarica, Cassia auriculata leaf extract, Geranium leaf extract, Ficus benghalensis leaf extract, Aqueous fruit extract of Syzygium alternifolium, fruit extract of Sambucus nigra [33,34]
3.Chemical reductionDMF, NaBH4, Trisodium citrate, ascorbic acid, dextrose,
ethylene glycol, glucose.

Table 3.

Sources used for synthesis of AgNP.

The synthesis of AgNPs can also be done by utilizing other physical methods such as evaporation-condensation and laser ablation, UV-initiated photo reduction, electrochemical synthetic method, irradiation methods [35]. Studies concluded that geometric mean diameter, shape, pH, and source for synthesis of AgNPs influence their efficiency. The synthesized AgNP can be characterized using UV-visible spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy for their structural properties. Although AgNPs were remarkably noted for their potential in pathogenic control, their effect on EPS has not been given sufficient attention [36].

8.2 Natural compounds as antibiofilm agents

Herbal compound aids the determination of novel constituents with interesting structures and biological activity. The antibiofilm properties of natural products rely on the inhibition of polymer matrix formation, resisting cell adhesion and attachment, breaking in ECM generation, and reducing virulence factors generation, thereby obstructing QS network and biofilm development [37]. The natural compounds that possess antibiofilm properties can be broadly classified into phenolics, essential oils, terpenoids, lectins, alkaloids, polypeptides, and polyacetylenes [38]. They either act merely or synergistically by different mechanisms. Various researches have been carried out with natural products that are discussed below:

8.2.1 Garlic

Allium sativum L has been extensively used in treating numerous diseases such as wound infection, malaria, common cold, sexually transmitted diseases [39]. Garlic possibly has a QS-interfering compound. DNA microarray analysis disclosed that Ajoene, a garlic-derived sulfur-containing compound, restricted QS-regulated gene expression in P. aeruginosa. Reasonable designing and biological screening of all compounds from garlic was carried out, resulting in the identification of a potent QS inhibitor N-(heptylsulfanylacetyl)-l-homoserine lactone. This element was found to disrupt the QS signaling by inhibiting transcriptional regulators LuxR and LasR. Recent studies have proved the antiswarming, anti-adherence, and antibiofilm activity of the aquatic extracts of garlic [40]. Ethanolic and methanolic extracts of garlic against six different bacterial species (Escherichia coli, Staphylococcus aureus, Bacillus cereus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Klebsiella pneumonia) show antibacterial activity at the concentration of 125–500 mg/mL through disc diffusion, and the A. sativum L extracts were potent enough restrict biofilm structures and the concentrations of each extract depend on the inhibitory effect [41].

8.2.2 Onion

Extracts of onion contains pharmaceutical properties that can be used as one of the promising therapies for the treatment of neoplastic, metabolic, and immunological diseases, which also involves bacterial, viral, and other fungal infections [42]. The anti-adherence, antibacterial, antibiofilm, and antimotility role of aqueous extracts of fresh or powdered onion and onion oil were studied from which the aqueous extracts of fresh and powdered onion showed more powerful inhibitory effects on biofilm than onion oil on the growth of both Gram-positive and Gram-negative bacteria [43]. Systematic assessment of quercetin, total phenolics, flavonoids, antioxidants, antibacterial, and antibiofilm or antibiofouling properties of methanolic extracts of fresh and aging onions of six varieties was studied by Kavitha et al., which concluded that the onions that had been stored for 3 months showed the best antibiofilm effects. The red variety of Allium cepa extract was found to have higher antimicrobial activity when compared with the white and yellow varieties. At the range of about 50 μg mL–1, the extracts were observed to reduce the biofilm growth of P. aeruginosa and S. aureus [44].

8.2.3 Rhubarb

Rhubarb is one of the most traditionally available medicinal materials included in Pharmacpoeia due it its bacteriostatic and anti-inflammatory properties. Emodin is the bioactive compound that has the ability to reverse multi-drug resistance. Natural emodin is obtained from Rheum palmatum L., Rheum tanguticum Maxim ex Balf, and Rheum ocinale [44]. Yan et al. studied the activity of emodin against S. aureus biofilm and confirmed the molecular mechanism that they decrease the release of eDNA and represses the biofilm-forming genes such as cidA, icaA, dltB, agrA, sortaseA, and sarA [45].

8.2.4 Banana

Studies concluded the antibacterial properties of banana in traditional medicine across the world. Generally, stem juice, flowers, and fruits of the banana plant are utilized for treating diarrhea and dysentery [46]. Vijayakumar et al. studied the antibiofilm properties of Musa acuminata Colla. against P. aeruginosa and described the mechanism of inhibiting the secretion of biofilm proteins and cell surface hydrophobicity productions [47].

8.2.5 Ginger

Ginger had been used in food and medicine for thousand years with the evidence demonstrating that it has antibacterial activity against the commercially available antibiotics by inhibiting QS signaling pathway [48]. Kim et al. initially investigated the inhibition of biofilm with ginger extract in P. aeruginosa. The biofilm assay demonstrated that the ginger extract decreased the biofilm development by 39–56% by reducing the formation of extracellular polymeric substances (EPS), which was associated with the suppression in secondary messenger, bis-(3c-5c)-cyclic dimericguagranosine [49]. Studies have shown that ginger essential oil at the biofilm inhibitory concentration (BIC) of 1.56 μL mL−1, S. aureus had 94% inhibition of biofilm, and at BIC 0.78 μL mL−1Enterococcus faecalis, K. pneumonia, and E. coli showed 91, 89, and 83% inhibition of biofilm [50].

Table 4 enlists the natural compounds with antibiofilm activity.

S.NoSourceActive compoundMechanism of action
1.Origanum vulgare (oregano)CarvacrolPost-translational inhibition againstlasI, which effects N- acyl-homoserine lactone secretion. It mostly acts on QS machinery against P. aeruginosa [51].
2.Apis mellifera (Honey)Defensin-1Manuka and Honey dew significantly reduce cell viability of S. aureus, P. aeruginosa, S. agalactia [52]
3.Curcuma longa L (Turmeric)CurcuminRestricts pellicle formation, Pilli motility and ring biofilm formation by interaction with biofilm response regulator BfmR [53].
4.Camellia sinesis (L)Epigallocatechin-3-gallateReduce the curli production and expression of curli-related proteins csgA, csgB, and csgD increases the degradation of sigma factor (RpoS) by ClpXP protease [54].
5.Capsicum annum (Bell pepper)Capsicum storage peptide 37 (CSP37)Inhibited the formation and development of biofilm in common pathogenic strains at the concentration of 5 and 10 mg/ml through CSP [55].

Table 4.

Natural compounds with antibiofilm activity.


9. Conclusion

In recent times, the concept of biofilm has influenced almost every treatment step of infection due to high level of protection against antibiotics and antimicrobial agents, being the thrust to human medical management. Hence, there is a crucial demand to develop novel strategies to surpass the antibiotic resistance after understanding the clear mechanisms behind it. The plant compounds, phytochemicals, and nanoparticles can be fused with antimicrobial agents, which have substantial research evidence for their antibiofilm effects through their synergism. In spite of the clinical trials being done on such compounds, further study is required to prove their safety and effectiveness to support the clinical systems.



We would like to thank our principal Dr.M. Ramanathan D.Sc., for providing us with sufficient facilities to complete this book chapter.

Conflict of interest

The authors declare no conflict of interest.


  1. 1. Chandki R, Banthia P, Banthia R. Biofilms: A microbial home. Journal of Indian Society of Periodontology. 2011;15(2):111-114. DOI: 10.4103/0972-124X.84377
  2. 2. Wyatt JE, Hesketh LM, Handley PS. Lack of correlation between fibrils, hydrophobicity and adhesion for strains of streptococcus sanguis biotypes 1 and 2. Microbios. 1987;50:7-15. DOI: 10.3109/08910609109140265
  3. 3. Harty Derek WS, Handley PS. Expression of the surface properties of the fibrillar Streptococcus salivarius HB and its adhesion deficient mutants grown in continuous culture under glucose limitation. Journal of General Microbiology. 1989;135:11-21. DOI: 10.1099/00221287-135-10-2611
  4. 4. Heukelekian H, Heller A. Relation between food concentration and surface for bacterial growth. Journal of Bacteriology. 1940;40:547-558. DOI: 10.1128/jb.40.4.547-558
  5. 5. Jamal M, Tasneem U, Hussain T, Andleeb S. Bacterial biofilm: Its composition, formation and role in human infections. Journal of Microbiology and Biotechnology. 2015;4(3):1-14. DOI: 10.1016/j.jcma.2017.07.012
  6. 6. Mah T-F. Biofilm-specific antibiotic resistance. Future Microbiology. 2012;7:1061-1072. DOI: 10.2217/fmb.12.76
  7. 7. Donlan RM. Biofilms and device-associated infections. Emerging Infectious Disease. 2001;7:277-281. DOI: 10.3201/eid0702.010226
  8. 8. Donlan RM, Costerton JW. Biofilms: Survival mechanisms of clinically relevant microorganisms. Clinical Microbiology Review. 2002;15:167-193. DOI: 10.1128/CMR.15.2.167-193.2002
  9. 9. Maki DG, Mermel LA. Infections due to infusion therapy. In: Hospital Infections. 4th ed. Philadelphia: Lippincott-Raven; 1998. pp. 689-724. DOI: 10.1067/SO 196-6553(03)00703-X
  10. 10. Braunwald E. Valvular heart disease. In: Heart Disease. 5th ed. Vol. 2. Philadelphia: W.B. Saunders Co; 1997. pp. 1007-1066. DOI: 10.4065%2Fmcp.2009.0706
  11. 11. Kokare CR, Chakraborty S, Khopade AN, Mahadik KR. Biofilm importance and applications. Indian Journal of Biotechnology. 2009;8:159-168. Available from:
  12. 12. Sharma D, Misba L, Khan AU. Antibiotics versus biofilm: An emerging battleground in microbial communities. Antimicrobial Resistance and Infection Control. 2019;8(76):1-10. DOI: 10.1186/s13756-019-0533-3
  13. 13. Wilkins M, Hall-Stoodley L, Allan RN, Faust SN. New approaches to the treatment of biofilm-related infections. Journal of Infection. 2014;69(1):47-52. DOI: 10.1016/j.jinf.2014.07.014
  14. 14. Lazar V. Quorum sensing in biofilms: How to destroy the bacterial citadels or their cohesion/power? Anaerobe. 2011;17:280-285. DOI: 10.1016/j.anaerobe.2011.03.023
  15. 15. Sharma D, Misba L, Khan AU. Antibiotics versus biofilm; an emerging battle ground in microbial communities. Antimicrobial Resistance and Infection Control. 2019;8(1):76. DOI: 10.1186/s13756-019-0533-3
  16. 16. Lewis K. Persister cells. Annual Review of Microbiology. 2010;62:357-372. DOI: 10.1146/annurev.micro.112408.134306
  17. 17. Hall-Stoodley L et al. Bacterial biofilms: From the natural environment to infectious diseases. Nature Reviews Microbiology. 2004;2:95-108. DOI: 10.1038/nrmicro821
  18. 18. Saleh T. Detection: From electrochemistry to spectroscopy with chromatographic techniques. Recent Trends with Nanotechnology Scientific Research. 2014;2:27-32. DOI: 10.4236/detection.2014.24005
  19. 19. Ansari SA, Husain Q , Qayyum S, Azam A. Designing and surface modification of zinc oxide nanoparticles for biomedical applications. Food and Chemical Toxicology. 2011;49:2107-2115. DOI: 10.1016/j.fct.2011.05.025
  20. 20. Qayyum S, Khan AU. Nanoparticles vs biofilm; a battle against another paradigm of antibioitic resistance. Medicinal Chemistry Communications. 2016;7:1479-1498. DOI: 10.1039/D1MA00639H
  21. 21. Kammari R, Das NG, Das SK. Chapter 6 - Nanoparticulate systems for therapeutic and diagnostic applications. In: Micro and Nano Technologies, Emerging Nanotechnologies for Diagnostics, Drug Delivery and Medical Devices. O REILLY; 2017. pp. 105-144. DOI: 10.1016/B978-0-323-42978-8.00006-1
  22. 22. Ramasamy MK, Lee J. Recent nanotechnology approaches for prevention and treatment of biofilm-associated infections on medical device. BioMedical Research International. 2016;31:1-18. DOI: 10.1155/2016/1851242
  23. 23. Chaudhary S, Jyoti A, Shrivastava V, Tomar RS. Role of nanoparticles as antibiofilm agents: A comprehensive review. Current Trends in Biotechnology and Pharmacy. 2020;2014:97-110. DOI: 10.5530/ctbp.2020.1.10
  24. 24. Tran HM, Tran H, Booth MA, Fox KE, Nguyen TH, Tran N, et al. Nanomaterials for treating bacterial biofilms on implantable medical devices. Nanomaterials. 2020;10:1-19. DOI: 10.3390/nano10112253
  25. 25. Taylor EN, Webster TJ. The use of super paramagnetic nanoparticles for prosthetic biofilm prevention. International Journal of Nanomedicine. 2009;4:145-152. PMCID: PMC2747349
  26. 26. Agarwala M, Choudhury B, Yadav RNS. Comparative study of antibiofilm activity of copper oxide and iron oxide nanoparticles against multidrug resistant biofilm forming uropathogens. Indian Journal of Microbiology. 2014;54:365-368. DOI: 10.1007%2Fs12088-014-0462-z
  27. 27. Ikuma K, Madden AS, Decho AW, Lau BLT. Deposition of nanoparticles onto polysaccharide-coated surfaces: Implications for nanoparticle–biofilm interactions. Environmental Science. Nano. 2014;1:117-122. DOI: 10.3389/fmicb.2015.00677
  28. 28. Shkodenko L, Kassirov I, Koshel E. Metal oxide nanoparticles against bacterial biofilms: Perspectives and limitations. Microorganisms. 2020;8(10):1545. DOI: 10.3390/microorganisms8101545
  29. 29. Kishore MY, Kunal B, Kumar JS, Abeer H, Fathi AAE, Kumar MT. Anti-biofilm and antibacterial activities of silver nanoparticles synthesized by the reducing activity of phytoconstituents present in the indian medicinal plants. Frontiers in Microbiology. 2020;11:1143. DOI: 10.3389/fmicb.2020.01143
  30. 30. John MS, Nagoth JA, Ramasamy KP, Mancini A, Giuli G, et al. Synthesis of bioactive silver nanoparticles by a pseudomonas strain associated with the antarctic psychrophilic protozoon Euplotes focardii. Marine Drugs. 2020;18:38. DOI: 10.3390/md18010038
  31. 31. Yusof HM, Rahman N’AA, Mohamad R, Zaidan UH. Microbial mediated synthesis of silver nanoparticles by lactobacillus plantarum TA4 and its antibacterial and antioxidant activity. Applied Sciences. 2020;10:6973. DOI: 10.3390/app10196973
  32. 32. Othman AM, Elsayed MA, Al-Balakocy NG, Hassan MM, Elshafei AM. Biosynthesis and characterization of silver nanoparticles induced by fungal proteins and its application in different biological activities. Journal of Genetic and Engineering and Biotechnology. 2020;17(8):7. DOI: 10.1186/s43141-019-0008-1
  33. 33. Iravani S, Korbekandi H, Mirmohammadi SV, Zolfaghari B. Synthesis of silver nanoparticles: Chemical, physical and biological methods. Research in Pharmaceutical Sciences. 2014;9(6):385-406
  34. 34. Alabdallah NM, Hasan MM. Plant-based green synthesis of silver nanoparticles and its effective role in abiotic stress tolerance in crop plants. Saudi Journal of Biological Sciences. 2021;28(10):5631-5639. DOI: 10.1016/j.sjbs.2021.05.081
  35. 35. Kruis F, Fissan H, Rellinghaus B. Sintering and evaporation characteristics of gas-phase synthesis of size-selected PbS nanoparticles. Materials Science and Engineering. 2000;69:329-334. DOI: 10.1016/S0921-5107(99)00298-6
  36. 36. Siddique MH, Aslam B, Imran M, Ashraf A, Nadeem H, Hayat S, et al. Effect of silver nanoparticles on biofilm formation and eps production of multidrug–resistant Klebsiella pneumoniae. Biomedical Research International. 2020;19:1-9. DOI: 10.1155/2020/6398165
  37. 37. Hoyle BD, Jass J, Costerton JW. The biofilm glycocalyx as a resistance factor. Journal of Antimicrobial Chemotherapy. 1990;26(1):1-5. DOI: 10.1093/jac/26.1.1
  38. 38. Mishra R, Panda A k, De Mandal S, Shakeel M, Bisht SS, Khan J. Natural anti-biofilm agents: Strategies to control biofilm – Forming pathogens. Frontiers in Microbiology. 2020;11:1-23. DOI: 10.3389/fmicb.2020.566325
  39. 39. Tessema B, Mulu A, Kassu A, Yismaw G. An in vitro assessment of the antibacterial effect of garlic (Allium sativum) on bacterial isolates from wound infections. Ethiopian Medical Journal. 2006;44(4):385-389
  40. 40. Hindi NKK, Al-Dabbagh NN, Dil Ghani Chabuck ZA. Anti-swarming, anti-adherence and anti-biofilm activities of garlic-related aquatic extracts: An in vitro study. Asian Journal of Microbiology Biotechnology and Environmental Sciences. 2018;20(2):137-147. DOI: 10.3390/molecules25235486
  41. 41. Zeinab M, Mehdi H. The effects of extracts on biofilm formation and activities of six pathogenic bacteria, Jundishapur. Journal of Microbiology. 2015;8(8):1-7. DOI: 10.5812/jjm.18971v2
  42. 42. Hamid NO, Mohammed Abdul-Hassan AL-Z, Nada KKH. An invitro study of anti-bacterial, anti-adherence, anti biofilm and anti-motility activities of the aqueous extracts of fresh and powdered onion and onion oil. International Journal of Pharmaceutical Science and Research. 2018;10(6):1573-1578. DOI: 10.1111/j.1365-2672.2008.03882.x
  43. 43. Kavita S, Neelima M, Yong RL. Systematic study on active compounds as antibacterial and antibiofilm agent in aging onions. Journal of Food and Drug Analysis. 2018;26:518-528. DOI: 10.1016/j.jfda.2017.06.009
  44. 44. Yang T, Bai J, Yu Y, Bai X, Bello-Onaghise G, Xu Y, et al. Intervene effect on Streptococcus suis biofilm formation of emodin extracted from Rheum ocinale baill. Research Square. 2020:1-33. DOI: 10.3389/fphar.2018.00227
  45. 45. Yan X, Gu S, Shi Y, Cui X, Wen S, Ge J. The effect of emodin on Staphylococcus aureus strains in planktonic form and biofilm formation in vitro. Archives of Microbiology. 2017;199(9):1267-1275. DOI: 10.1007/s00203-017-1396-8
  46. 46. Jouneghani RS, Castro AHF, Panda SK, Swennen R, Luyten W. Antimicrobial activity of selected banana cultivars against important human pathogens, including Candida biofilm. Food. 2020;435(9):1-19. DOI: 10.3390/foods9040435
  47. 47. Vijayakumar K, Ramanathan T. Musa acuminata and its bioactive metabolite 5-hydroxymethylfurfural mitigates quorum sensing (las and rhl) mediated biofilm and virulence production of nosocomial pathogen Pseudomonas aeruginosa in vitro. Journal of Ethnopharmacology. 2019;246:112242. DOI: 10.1016/j.jep.2019.112242
  48. 48. Sebiomo A, Awofodu AD, Awosanya AO, Awotona FE, Ajayi AJ. Comparative studies of antibacterial effect of some antibiotics and ginger on two pathogenic bacteria. Journal of Microbiology and Antimicrobials. 2011;3:18-22. DOI: 10.1155/2014/562804
  49. 49. Kim H-S, Park H-D. Ginger extract inhibits biofilm formation by P.aeruginosa PA14. PLoS One. 2013;8(9):1-16. DOI: 10.1371/journal.pone.0076106
  50. 50. Aradhana D, Suchanda D, Rajesh KS, Saubhagini S, Enketeswara S. Antibiofilm and antibacterial activity of essential oil bearing Zingiber offcinalis Rosc.(ginger) rhizome against multi-drug resistant isolates. Journal of Essential Oil Bearing Plants. 2019;22(4):1163-1171. DOI: 10.1080/0972060X.2019.1683080
  51. 51. Tapia-Rodriguez MR, Bernal-Mercado AT, Gutierrez-Pacheco MM, Vazquez-Armenta FJ, Hernandez-Mendoza A, Gonzalez-Aguilar GA, et al. Virulence of Pseudomonas aeruginosa exposed to carvacrol: Alterations of the quorum sensing at enzymatic and gene levels. Journal of Cell Communication and Signalling. 2019;13:531-537. DOI: 10.1007/s12079-019-00516-8
  52. 52. Allen KL, Molan PC, Reid GM. The variability of the antibacterial activity of honey. Apiacta. 1991;26:114-121. DOI: 10.1371%2Fjournal.pone.0018229
  53. 53. Raorane CJ, Lee JH, Kim YG, Rajasekharan SK, Garcia-Contreras R, Lee J. Antibiofilm and antivirulence efficacies of flavonoids and curcumin against Acinetobacter baumannii. Frontiers in Microbiology. 2019;10:990. DOI: 10.3389/fmicb.2019.00990
  54. 54. Arita-Morioka KI, Yamanaka K, Mizunoe Y, Tanaka Y, Ogura T, Sugimoto S. Inhibitory effects of Myricetin derivatives on curli dependent biofilm formation in Escherichia coli. Scientific Reports. 2019;8:8452. DOI: 10.1038/s41598-018-26748-z
  55. 55. Borowski RGV, Barros MP, Da Silva DB, Lopes NP, Zimmer KR, Staats CC, et al. Red peptide coatings control S. epidermis biofilm formation. International Journal of Pharmaceutics. 2020;574:1-11. DOI: 10.1016/j.ijpharm.2019.118872

Written By

Sankar Veintramuthu and Selliamman Ravi Mahipriya

Submitted: 23 January 2022 Reviewed: 11 March 2022 Published: 30 April 2022