Abstract
The rise in global antibiotic resistance is a significant concern, further intensified by the increasing prevalence of organisms that form biofilms. Biofilms are highly organised communities of microorganisms, including bacteria and fungi, comprising a mixture of strains forming a slimy extracellular matrix of extracellular polymeric substances. They could be found on biotic and abiotic surfaces. Infections associated with biofilms have been reported to be linked to treatment failure, increased cost of treatment, prolonged hospital stay and increased morbidity and mortality. The biofilm serves as a protective shield for organisms in the matrix, making them highly resistant to antibiotics, disinfectants, mechanical fluctuations, and immune response. This review aims to describe the process of its formation, clinical implications, methods of detection and preventive strategies.
References
[1]. Schulze A, Mitterer F, Pombo JP, Schild S. Biofilms by bacterial human pathogens: Clinical relevance - development, composition and regulation - therapeutical strategies. Microbial Cell [Internet]. 2021 Feb 1;8(2):28–56. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841849/
[2]. Tang KWK, Millar BC, Moore JE. Antimicrobial Resistance (AMR). British Journal of Biomedical Science. 2023 Jun 28;80(11387):11387.
[3]. Lai CKC, Ng RWY, Leung SSY, Hui M, Ip M. Overcoming the rising incidence and evolving mechanisms of antibiotic resistance by novel drug delivery approaches – An overview. Advanced Drug Delivery Reviews. 2022 Feb; 181:114078.
[4]. World Health Organization. Antimicrobial Resistance [Internet]. World Health Organization. World Health Organization; 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
[5]. Banthia R, Chandki R, Banthia P. Biofilms: A microbial home. Journal of Indian Society of Periodontology [Internet]. 2011;15(2):111. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183659/
[6]. Armbruster CR, Parsek MR. New insight into the early stages of biofilm formation. Proceedings of the National Academy of Sciences. 2018 Apr 9;115(17):4317–9.
[7]. Samrot AV, Abubakar Mohamed A, Faradjeva E, Si Jie L, Hooi Sze C, Arif A, et al. Mechanisms and Impact of Biofilms and Targeting of Biofilms Using Bioactive Compounds-A Review. Medicina (Kaunas, Lithuania) [Internet]. 2021 Aug 18;57(8):839. Available from: https://pubmed.ncbi.nlm.nih.gov/34441045/
[8]. Zhao A, Sun J, Liu Y. Understanding bacterial biofilms: From definition to treatment strategies. Frontiers in Cellular and Infection Microbiology [Internet]. 2023 Apr 6;13(1137947). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117668/
[9]. Khalid SJ, Ain Q, Khan SJ, Jalil A, Siddiqui MF, Ahmad T, Badshah M, Adnan F. Targeting Acyl Homoserine Lactones (AHLs) by the quorum quenching bacterial strains to control biofilm formation in Pseudomonas aeruginosa. Saudi J Biol Sci. 2022 Mar;29(3):1673-1682. doi: 10.1016/j.sjbs.2021.10.064. Epub 2021 Oct 30. PMID: 35280554; PMCID: PMC8913397.
[10]. Alonso V, Paula M, Airlane F, Giovana Rueda Barboza, Liliana, Cirone C. Dry surface biofilms in the food processing industry: An overview on surface characteristics, adhesion and biofilm formation, detection of biofilms, and dry sanitization methods. Comprehensive Reviews in Food Science and Food Safety. 2022 Dec 5;22(1):688–713.
[11]. Bera JH, Selvin L, Gang S, Patel DN. Biofilm. Elsevier eBooks. 2023 Jan 1;369–90.
[12]. Hari Prasath Nagaiah, Karthikeyan Kandaswamy, Arumugam Priya, Thirupathi Kasthuri, Pandian SK. Biofilms associated with biomedical implants and combating therapies. Elsevier eBooks. 2023 Jan 1;335–53.
[13]. Singh S, Datta S, Narayanan KB, Rajnish KN. Bacterial exo-polysaccharides in biofilms: role in antimicrobial resistance and treatments. Journal of Genetic Engineering and Biotechnology. 2021 Sep 23;19(1).
[14]. None Vandana, Das S. Structural and mechanical characterization of biofilm-associated bacterial polymer in the emulsification of petroleum hydrocarbon. 3 Biotech. 2021 Apr 25;11(5).
[15]. Sharma S, Mohler J, Mahajan SD, Schwartz SA, Bruggemann L, Aalinkeel R. Microbial Biofilm: A Review on Formation, Infection, Antibiotic Resistance, Control Measures, and Innovative Treatment. Microorganisms [Internet]. 2023 Jun 1;11(6):1614. Available from: https://www.mdpi.com/2076-2607/11/6/1614
[16]. Quan K, Hou J, Zhang Z, Ren Y, Peterson BW, Flemming HC, et al. Water in bacterial biofilms: pores and channels, storage and transport functions. Critical Reviews in Microbiology. 2021 Aug 19;48(3):283–302.
[17]. Galdino RV, Benevides CA, Tenório RP. Diffusion maps of Bacillus subtilis biofilms via magnetic resonance imaging highlight a complex network of channels. Colloids and Surfaces B Biointerfaces. 2020 Feb 26; 190:110905–5.
[18]. Karygianni L, Ren Z, Koo H, Thurnheer T. Biofilm Matrixome: Extracellular Components in Structured Microbial Communities. Trends in Microbiology [Internet]. 2020 Apr 21;28(8). Available from: https://reader.elsevier.com/reader/sd/pii/S0966842X20300871?token=564D8AA0AA908F18D732CD6AF9D12300BF0B1A1A2B360A6B9926B8FC840CFCF4260A7B1127A772152BDC7B17C66B93B0
[19]. Molina-Santiago C, de Vicente A, Romero D. Bacterial extracellular matrix as a natural source of biotechnologically multivalent materials. Computational and Structural Biotechnology Journal [Internet]. 2021 Jan 1; 19:2796–805. Available from: https://www.sciencedirect.com/science/article/pii/S2001037021001896
[20]. Singh A, Puneet Singh Chauhan. Ecological Significance of Soil-Associated Plant Growth-Promoting Biofilm-Forming Microbes for Stress Management. 2017 Jul 21;291–326.
[21]. Awuor SO, Omwenga EO, Mariita RM, Daud II. Cholera outbreak: antibiofilm activity, profiling of antibiotic-resistant genes and virulence factors of toxigenic Vibrio cholerae isolates reveals concerning traits. Access Microbiology. 2022 Mar 23;4(3).
[22]. Jamal M, Ahmad W, Andleeb S, Jalil F, Imran M, Nawaz MA, et al. Bacterial biofilm and associated infections. Journal of the Chinese Medical Association: JCMA. 2018;81(1):7–11.
[23]. Sharma D, Misba L, Khan AU. Antibiotics versus biofilm: an Emerging Battleground in Microbial Communities. Antimicrobial Resistance & Infection Control. 2019 May 16;8(1).
[24]. Zheng S, Bawazir M, Dhall A, Kim HE, He L, Heo J, et al. Implication of Surface Properties, Bacterial Motility, and Hydrodynamic Conditions on Bacterial Surface Sensing and Their Initial Adhesion. Frontiers in Bioengineering and Biotechnology. 2021 Feb 12;9.
[25]. Rather MA, Gupta K, Mandal M. Microbial biofilm: formation, architecture, antibiotic resistance, and control strategies. Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology] [Internet]. 2021 Dec 1;52(4):1701–18. Available from: https://pubmed.ncbi.nlm.nih.gov/34558029/
[26]. Mirghani R, Saba T, Khaliq H, Mitchell J, Do L, Chambi L, et al. Biofilms: Formation, drug resistance and alternatives to conventional approaches. AIMS Microbiology [Internet]. 2022;8(3):239–77. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9576500/
[27]. Preda VG, Săndulescu O. Communication is the key: biofilms, quorum sensing, formation and prevention. Discov d eries [Internet]. 2019 Sep 30;7(3):e10. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086079/
[28]. Sauer K, Stoodley P, Goeres DM, Hall-Stoodley L, Burmølle M, Stewart PS, et al. The biofilm life cycle: expanding the conceptual model of biofilm formation. Nature Reviews Microbiology [Internet]. 2022 Oct 1;20(10):608–20. Available from: https://www.nature.com/articles/s41579-022-00767-0#citeas
[29]. Boban T, Nadar S, Tauro S. Breaking down bacterial communication: a review of quorum quenching agents. Future Journal of Pharmaceutical Sciences. 2023 Aug 30;9(1).
[30]. Abebe GM. The Role of Bacterial Biofilm in Antibiotic Resistance and Food Contamination. International Journal of Microbiology. 2020 Aug 25; 2020:1–10.
[31]. De Oliveira DMP, Forde BM, Kidd TJ, Harris PNA, Schembri MA, Beatson SA, et al. Antimicrobial resistance in ESKAPE pathogens. Clinical Microbiology Reviews. 2020 May 13;33(3).
[32]. Vale de Macedo GHR, Costa GDE, Oliveira ER, Damasceno GV, Mendonça JSP, Silva L dos S, et al. Interplay between ESKAPE Pathogens and Immunity in Skin Infections: An Overview of the Major Determinants of Virulence and Antibiotic Resistance. Pathogens. 2021 Feb 2;10(2):148.
[33]. Banawas SS, Alobaidi AS, Dawoud TM, AlDehaimi A, Alsubaie FM, Abdel-Hadi A, et al. Prevalence of Multidrug-Resistant Bacteria in Healthcare-Associated Bloodstream Infections at Hospitals in Riyadh, Saudi Arabia. Pathogens [Internet]. 2023 Sep 1;12(9):1075. Available from: https://www.mdpi.com/2076-0817/12/9/1075
[34]. Wi YM, Patel R. Understanding Biofilms and Novel Approaches to the Diagnosis, Prevention, and Treatment of Medical Device-Associated Infections. Infectious Disease Clinics of North America [Internet]. 2018 Dec;32(4):915–29. Available from: https://mayoclinic.pure.elsevier.com/en/publications/understanding-biofilms-and-novel-approaches-to-the-diagnosis-prev
[35]. Sterzenbach T, Helbig R, Hannig C, Hannig M. Bioadhesion in the oral cavity and approaches for biofilm management by surface modifications. Clinical Oral Investigations. 2020 Oct 27;24(12):4237–60.
[36]. Abdelhamid AG, Yousef AE. Combating Bacterial Biofilms: Current and Emerging Antibiofilm Strategies for Treating Persistent Infections. Antibiotics [Internet]. 2023 Jun 3;12(6):1005. Available from: https://mdpi-res.com/antibiotics/antibiotics-12-01005/article_deploy/antibiotics-12-01005-v2.pdf?version=1685940502
[37]. Vestby LK, Grønseth T, Simm R, Nesse LL. Bacterial Biofilm and Its Role in the Pathogenesis of Disease. Antibiotics [Internet]. 2020 Feb 3;9(2):59. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167820/
[38]. Kamineni S, Huang C. The antibacterial effect of sonication and its potential medical application. SICOT-J [Internet]. 5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572995/
[39]. Ioana Roxana Codru, Sava M, Bogdan Ioan Vintilă, Alina Simona Bereanu, Bîrluțiu V. A Study on the Contributions of Sonication to the Identification of Bacteria Associated with Intubation Cannula Biofilm and the Risk of Ventilator-Associated Pneumonia. Medicina. 2023 May 31;59(6):1058–8.
[40]. Frickmann H, Zautner AE, Moter A, Kikhney J, Hagen RM, Stender H, et al. Fluorescencein situhybridization (FISH) in the microbiological diagnostic routine laboratory: a review. Critical Reviews in Microbiology. 2017 Jan 27;43(3):263–93.
[41]. Franco-Duarte R, Černáková L, Kadam S, S. Kaushik K, Salehi B, Bevilacqua A, et al. Advances in Chemical and Biological Methods to Identify Microorganisms—From past to Present. Microorganisms [Internet]. 2019 May 13;7(5):130. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6560418/
[42]. Costa-Orlandi C, Sardi J, Pitangui N, de Oliveira H, Scorzoni L, Galeane M, et al. Fungal Biofilms and Polymicrobial Diseases. Journal of Fungi [Internet]. 2017 May 10;3(2):22. Available from: https://dx.doi.org/10.3390%2Fjof3020022
[43]. Relucenti M, Familiari G, Donfrancesco O, Taurino M, Li X, Chen R, et al. Microscopy Methods for Biofilm Imaging: Focus on SEM and VP-SEM Pros and Cons. Biology [Internet]. 2021 Jan 12;10(1). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828176/
[44]. Walker JN, Flores-Mireles AL, Lynch AJL, Pinkner C, Caparon MG, Hultgren SJ, et al. High-resolution imaging reveals microbial biofilms on patient urinary catheters despite antibiotic administration. World Journal of Urology. 2019 Dec 2;
[45]. Cleaver L, Garnett JA. How to study biofilms: technological advancements in clinical biofilm research. Frontiers in cellular and infection microbiology. 2023 Dec 13;13.
[46]. Songtanin B, Peterson CJ, Molehin AJ, Nugent K. Biofilms and Benign Colonic Diseases. International Journal of Molecular Sciences. 2022 Nov 17;23(22):14259.
[47]. Shenoy V, Harika K, Narasimhaswamy N, Chawla K. Detection of biofilm production and its impact on antibiotic resistance profile of bacterial isolates from chronic wound infections. Journal of Global Infectious Diseases. 2020;12(3):129.
[48]. Jain S. Can EDTA Change MRSA into MSSA? A Future Prospective! JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH [Internet]. 2016; Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800529/
[49]. Allkja J, van Charante F, Aizawa J, Reigada I, Guarch-Pérez C, Vazquez-Rodriguez JA, et al. Interlaboratory study for the evaluation of three microtiter plate-based biofilm quantification methods. Scientific Reports [Internet]. 2021 Jul 2;11(1). Available from: htt ps://www.nature.com/articles/s41598-021-93115-w.pdf
[50]. Eladawy M, El-Mowafy M, El-Sokkary MMA, Barwa R. Effects of Lysozyme, Proteinase K, and Cephalosporins on Biofilm Formation by Clinical Isolates of Pseudomonas aeruginosa. Interdisciplinary Perspectives on Infectious Diseases [Internet]. 2020 Feb 8;2020:e6156720. Available from: https://www.hindawi.com/journals/ipid/2020/6156720/
[51]. Katongole P, Nalubega F, Florence NC, Asiimwe B, Andia I. Biofilm formation, antimicrobial susceptibility and virulence genes of Uropathogenic Escherichia coli isolated from clinical isolates in Uganda. BMC Infectious Diseases [Internet]. 2020 Jun 29;20(1). Available from: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05186-1
[52]. Cho JA, Roh YJ, Son HR, Choi H, Lee JW, Kim SJ, et al. Assessment of the biofilm-forming ability on solid surfaces of periprosthetic infection-associated pathogens. Scientific Reports [Internet]. 2022 Nov 4; 12:18669. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636376/
[53]. Sato Y, Ubagai T, Tansho-Nagakawa S, Yoshino Y, Ono Y. Effects of colistin and tigecycline on multidrug-resistant Acinetobacter baumannii biofilms: advantages and disadvantages of their combination. Scientific Reports [Internet]. 2021 Jun 3 [cited 2022 Oct 26];11(1). Available from: https://www.nature.com/articles/s41598-021-90732-3.pdf
[54]. Zhang S, Qu X, Jiao J, Tang H, Wang M, Wang Y, et al. Felodipine enhances aminoglycosides efficacy against implant infections caused by methicillin-resistant Staphylococcus aureus, persisters and biofilms. Bioactive Materials. 2022 Aug; 14:272–89.
[55]. Jha S, Anand S. Development and Control of Biofilms: Novel Strategies Using Natural Antimicrobials. Membranes. 2023 Jun 2;13(6):579.
[56]. Liu X, Yao H, Zhao X, Ge C. Biofilm Formation and Control of Foodborne Pathogenic Bacteria. Molecules [Internet]. 2023 Mar 7;28(6):2432. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058477/
[57]. Paluch E, Rewak-Soroczyńska J, Jędrusik I, Mazurkiewicz E, Jermakow K. Prevention of biofilm formation by quorum quenching. Applied Microbiology and Biotechnology. 2020 Jan 11;104(5):1871–81.
[58]. Sionov RV, Steinberg D. Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria. Microorganisms. 2022 Jun 16;10(6):1239.
[59]. Elsheredy A, El-Soudany I, Elsherbini E, Metwally D, Ghazal A. Effect of azithromycin and phenylalanine-arginine beta-naphthylamide on quorum sensing and virulence factors in clinical isolates of Pseudomonas aeruginosa. Iranian Journal of Microbiology. 2021 Feb 23;
[60]. Ryan Kaler KM, Nix JC, Schubot FD. RetS inhibits Pseudomonas aeruginosa biofilm formation by disrupting the canonical histidine kinase dimerization interface of GacS. Journal of Biological Chemistry [Internet]. 2021 Oct [cited 2022 Oct 24];297(4):101193. Available from: https://www.jbc.org/action/showPdf?pii=S0021-9258%2821%2900995-9
[61]. Abdel-Fatah SS, Mohammad NH, Elshimy Rana, Mosallam FM. Impeding microbial biofilm formation and Pseudomonas aeruginosa virulence genes using biologically synthesized silver Carthamus nanoparticles. Microbial Cell Factories. 2024 Sep 5;23(1).
[62]. Faisal S, Tariq MH, Abdullah N, Zafar S, Nisa ZU, Ullah R, et al. Bio synthesis, comprehensive characterization, and multifaceted therapeutic applications of BSA-Resveratrol coated platinum nanoparticles. Scientific Reports. 2024 Apr 3;14(1).
[63]. Mendes CR, Dilarri G, Forsan CF, Sapata V de MR, Lopes PRM, de Moraes PB, et al. Antibacterial action and target mechanisms of zinc oxide nanoparticles against bacterial pathogens. Scientific Reports. 2022 Feb 16;12(1).
[64]. Bari AK, Belalekar TS, Poojary A, Rohra S. Combination drug strategies for biofilm eradication using synthetic and natural agents in KAPE pathogens. Frontiers in Cellular and Infection Microbiology [Internet]. 2023 Apr 17; 13:1155699. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149696/
[65]. Shrestha L, Fan HM, Tao HR, Huang JD. Recent Strategies to Combat Biofilms Using Antimicrobial Agents and Therapeutic Approaches. Pathogens [Internet]. 2022 Feb 25;11(3):292. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955104/#:~:text=In%20general%2C%20two%20different%20strategies
[66]. Sikder A, Chaudhuri A, Mondal S, Singh P. Recent Advances on Stimuli-Responsive Combination Therapy against Multidrug-Resistant Bacteria and Biofilm. ACS applied bio materials. 2021 Jun 7;4(6):4667–83.
[67]. Sen CK, Roy S, Mathew-Steiner SS, Gordillo GM. Biofilm Management in Wound Care. Plastic & Reconstructive Surgery. 2021 Jul 27;148(2):275e288e.
[68]. Panebianco F, Rubiola S, Di Ciccio PA. The Use of Ozone as an Eco-Friendly Strategy against Microbial Biofilm in Dairy Manufacturing Plants: A Review. Microorganisms. 2022 Jan 13;10(1):162.
[69]. Ciarolla AA, Lapin N, Williams D, Chopra R, Greenberg DE. Physical Approaches to Prevent and Treat Bacterial Biofilm. Antibiotics. 2022 Dec 29;12(1):54.
[70]. Li Y, Qu Y, Yang H, Zhou X, Xiao P, Shao TL. Combatting biofilms in potable water systems: A comprehensive overview to ensuring industrial water safety. Environmental Microbiology Reports. 2023 Oct 12;15(6).
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