Biofilm formation and its regulation by extracellular appendages in Pseudomonas aeruginosa

Asma Ramzan, Tanzeela Rehman, Maria Sohail But, Mahnoor Imran, Uzma Qaisar


Pseudomonas aeruginosa is an infectious rod like bacterium which is equipped with a unique quorum-sensing system to sense the surrounding environment and communicate with bacterial cells in vicinity through excreting small molecules, called autoinducers. Quorum sensing system and autoinducer production are cellular density dependent mechanisms which are responsible for cell-cell signalling and regulating biological processes in this bacterium. P. aeruginosa is equipped with an arsenal of virulence factors and tools to protect it from toxins and host immune response which facilitate its survival in a wide range of habitats and environments. The most important virulence factor is biofilm which comprises of sessile community of bacteria covered with a matrix of polysaccharides and extracellular proteins offering enhanced resistance to antibiotics and host immune system. P. aeruginosa produces biofilms at a variety of infection sites in patients, on medical instruments and medical tools inside the patient body. It is very hard to eradicate and inhibit the formation of biofilms in immunocompromised patients. In this article, we described the stages of biofilm formation along with the role of various genetic and biochemical factors required for its formation. Special emphasis was given to extra-cellular appendages (flagella, pili and fimbriae) for their role in attachment of P. aeruginosa to the semi-solid serfaces and converting motile bacteria to sessile mode of life (biofilm). Moreover, polysaccharide matix formation and its resistance towards antibiotics is discussed. This review article can help in devising gene therapy strategies against biofilm formation and its eradication in nosocomial infections caused by drug resistant bacteria.


Biofilm; antibiotic resistance; P. aeruginosa; antibiotics; quorum sensing

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Aeschlimann, J. R., 2003. The role of multidrug efflux pumps in the antibiotic resistance of pseudomonas aeruginosa and other gram‐negative bacteria: Insights from the society of infectious diseases pharmacists. Pharmacotherapy: The Journal of human pharmacology and drug therapy, 23(7): 916-924.

Allison, K. R., M. P. Brynildsen and J. J. Collins, 2011. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature, 473(7346): 216-220.

Aloush, V., S. Navon-Venezia, Y. Seigman-Igra, S. Cabili and Y. Carmeli, 2006. Multidrug-resistant Pseudomonas aeruginosa: Risk factors and clinical impact. Antimicrobial agents and chemotherapy, 50(1): 43-48.

Asif, A., A. Iftikhar, A. Hamood, J. A. Colmer-Hamood and U. Qaisar, 2019. Isonitrile-functionalized tyrosine modulates swarming motility and quorum sensing in Pseudomonas aeruginosa. Microbial pathogenesis, 127: 288-295.

Botelho, J., F. Grosso and L. Peixe, 2019. Antibiotic resistance in Pseudomonas aeruginosa–mechanisms, epidemiology and evolution. Drug resistance updates, 44: 100640.

Burrows, L. L., 2012. Pseudomonas aeruginosa twitching motility: Type iv pili in action. Annual review of microbiology, 66(1): 493-520.

Davey, M. E., N. C. Caiazza and G. A. O'Toole, 2003. Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa pao1. Journal of bacteriology, 185(3): 1027-1036.

Diggle, S. P., S. Matthijs, V. J. Wright, M. P. Fletcher, S. R. Chhabra, I. L. Lamont, X. Kong, R. C. Hider, P. Cornelis and M. Cámara, 2007. The pseudomonas aeruginosa 4-quinolone signal molecules HHQ and PQS play multifunctional roles in quorum sensing and iron entrapment. Chemistry & biology, 14(1): 87-96.

Donlan, R. M. and J. W. Costerton, 2002. Biofilms: Survival mechanisms of clinically relevant microorganisms. Clinical microbiology reviews, 15(2): 167-193.

Driscoll, J. A., S. L. Brody and M. H. Kollef, 2007. The epidemiology, pathogenesis and treatment of Pseudomonas aeruginosa infections. Drugs, 67(3): 351-368.

Friedman, L. and R. Kolter, 2004. Genes involved in matrix formation in Pseudomonas aeruginosa pa14 biofilms. Molecular microbiology, 51(3): 675-690.

Gale, M. J., M. S. Maritato, Y. L. Chen, S. S. Abdulateef and J. E. Ruiz, 2015. Pseudomonas aeruginosa causing inflammatory mass of the nasopharynx in an immunocompromised hiv infected patient: A mimic of malignancy. IDCases, 2(2): 40-43.

Garrett, W. S., 2015. Cancer and the microbiota. Science, 348(6230): 80-86.

Gomila, A., E. Shaw, J. Carratalà, L. Leibovici, C. Tebé, I. Wiegand, L. Vallejo-Torres, J. M. Vigo, S. Morris, M. Stoddart, S. Grier, C. Vank, N. Cuperus, L. Van den Heuvel, N. Eliakim-Raz, C. Vuong, A. MacGowan, I. Addy and M. Pujol, 2018. Predictive factors for multidrug-resistant gram-negative bacteria among hospitalised patients with complicated urinary tract infections. Antimicrob resist infect control, 7: 111.

Hammond, A., J. Dertien, J. A. Colmer-Hamood, J. A. Griswold and A. N. Hamood, 2010. Serum inhibits p. Aeruginosa biofilm formation on plastic surfaces and intravenous catheters. Journal of surgical research, 159(2): 735-746.

Hentzer, M., G. M. Teitzel, G. J. Balzer, A. Heydorn, S. Molin, M. Givskov and M. R. Parsek, 2001. Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function. Journal of bacteriology, 183(18): 5395-5401.

Høiby, N., O. Ciofu, H. K. Johansen, Z. j. Song, C. Moser, P. Ø. Jensen, S. Molin, M. Givskov, T. Tolker‐Nielsen and T. Bjarnsholt, 2011. The clinical impact of bacterial biofilms. International journal of oral science, 3(2): 55-65.

Iftikhar, A., A. Asif, A. Manzoor, M. Azeem, G. Sarwar, N. Rashid and U. Qaisar, 2020. Mutation in pvcabcd operon of Pseudomonas aeruginosa modulates mexef-oprn efflux system and hence resistance to chloramphenicol and ciprofloxacin. Microbial pathogenesis, 149: 104491.

Kamble, E. and K. Pardesi, 2021. Antibiotic tolerance in biofilm and stationary-phase planktonic cells of Staphylococcus aureus. Microbial drug resistance, 27(1): 3-12.

Khalid, R., Q. Jaffar, A. Tayyeb and U. Qaisar, 2018. Peganum harmalapeptides (phamp) impede bacterial growth and biofilm formation in burn and surgical wound pathogens. Pakistan journal of pharmical science, 31(6): 2597-2605.

Kritsotakis, E. I., F. Kontopidou, E. Astrinaki, M. Roumbelaki, E. Ioannidou and A. Gikas, 2017. Prevalence, incidence burden, and clinical impact of healthcare-associated infections and antimicrobial resistance: A national prevalent cohort study in acute care hospitals in greece. Infection and drug resistance, 10: 317.

Kruczek, C., U. Qaisar, J. A. Colmer‐Hamood and A. N. Hamood, 2014. Serum influences the expression of pseudomonas aeruginosa quorum‐sensing genes and qs‐controlled virulence genes during early and late stages of growth. Microbiology open, 3(1): 64-79.

Kulasekara, H. D., I. Ventre, B. R. Kulasekara, A. Lazdunski, A. Filloux and S. Lory, 2005. A novel two‐component system controls the expression of Pseudomonas aeruginosa fimbrial cup genes. Molecular microbiology, 55(2): 368-380.

Lecuyer, S., R. Rusconi, Y. Shen, A. Forsyth, H. Vlamakis, R. Kolter and H. A. Stone, 2011. Shear stress increases the residence time of adhesion of pseudomonas aeruginosa. Biophysical journal, 100(2): 341-350.

Leid, J. G., C. J. Willson, M. E. Shirtliff, D. J. Hassett, M. R. Parsek and A. K. Jeffers, 2005. The exopolysaccharide alginate protects pseudomonas aeruginosa biofilm bacteria from ifn-γ-mediated macrophage killing. The journal of immunology, 175(11): 7512-7518.

Mikkelsen, H., M. Sivaneson and A. Filloux, 2011. Key two‐component regulatory systems that control biofilm formation in Pseudomonas aeruginosa. Environmental microbiology, 13(7): 1666-1681.

Mulani, M. S., E. E. Kamble, S. N. Kumkar, M. S. Tawre and K. R. Pardesi, 2019. Emerging strategies to combat eskape pathogens in the era of antimicrobial resistance: A review. Front microbiol, 10: 539.

Otton, L. M., M. da Silva Campos, K. L. Meneghetti and G. Corção, 2017. Influence of twitching and swarming motilities on biofilm formation in Pseudomonas strains. Archives of microbiology, 199(5): 677-682.

Pang, Z., R. Raudonis, B. R. Glick, T.-J. Lin and Z. Cheng, 2019. Antibiotic resistance in Pseudomonas aeruginosa: Mechanisms and alternative therapeutic strategies. Biotechnology advances, 37(1): 177-192.

Qaisar, U., L. Luo, C. L. Haley, S. F. Brady, N. L. Carty, J. A. Colmer-Hamood and A. N. Hamood, 2013. The pvc operon regulates the expression of the Pseudomonas aeruginosa fimbrial chaperone/usher pathway (cup) genes. PloS one, 8(4): e62735.

Qaisar, U., L. M. Luo, C. L. Haley, S. F. Brady, N. L. Carty, J. A. Colmer-Hamood and A. N. Hamood, 2013. The PVC operon regulates the expression of the Pseudomonas aeruginosa fimbrial chaperone/usher pathway (cup) genes. PloS one, 8(4).

Rasamiravaka, T., Q. Labtani, P. Duez and M. El Jaziri, 2015. The formation of biofilms by Pseudomonas aeruginosa: A review of the natural and synthetic compounds interfering with control mechanisms. BioMed research international, 2015:759348

Rashid, M. H. and A. Kornberg, 2000. Inorganic polyphosphate is needed for swimming, swarming, and twitching motilities of Pseudomonas aeruginosa. Proceedings of the national academy of sciences, 97(9): 4885-4890.

Schurek, K. N., E. Breidenstein and R. E. Hancock, 2012. Pseudomonas aeruginosa: A persistent pathogen in cystic fibrosis and hospital-associated infections. In: Antibiotic discovery and development. Springer: pp: 679-715.

Stewart, P. S. and J. W. Costerton, 2001. Antibiotic resistance of bacteria in biofilms. Lancet, 358(9276): 135-138.

Toyofuku, M., B. Roschitzki, K. Riedel and L. Eberl, 2012. Identification of proteins associated with the pseudomonas aeruginosa biofilm extracellular matrix. Journal of proteome research, 11(10): 4906-4915.

Vallet, I., J. W. Olson, S. Lory, A. Lazdunski and A. Filloux, 2001. The chaperone/usher pathways of Pseudomonas aeruginosa: Identification of fimbrial gene clusters (cup) and their involvement in biofilm formation. Proceedings of the national academy of sciences, 98(12): 6911-6916.

Wolska, K. I., A. M. Grudniak, Z. Rudnicka and K. Markowska, 2016. Genetic control of bacterial biofilms. Journal of applied genetics, 57(2): 225-238.

Xu, Y., L. H. Larsen, J. Lorenzen, L. Hall-Stoodley, J. Kikhney, A. Moter and T. R. Thomsen, 2017. Microbiological diagnosis of device-related biofilm infections. Apmis, 125(4): 289-303.



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