The Genetic Basis of Biofilm Formation in Acinetobacter baumannii and Its Clinical Implications
Abstract
Acinetobacter baumannii is an opportunistic pathogen known for its remarkable ability to form biofilms, contributing significantly to its persistence in hospital environments and resistance to antimicrobial treatments. Biofilm formation in A. baumannii is a complex, genetically regulated process involving a network of genes responsible for adhesion, extracellular matrix production, and stress response. Key genetic determinants include the bap gene, which encodes the biofilm-associated protein, the csu operon involved in pilus-mediated surface attachment, and the ompA gene, which enhances adhesion and immune evasion. Additionally, quorum sensing regulators such as abaI play a crucial role in coordinating biofilm development. The presence of these genetic elements not only enhances the pathogen’s ability to colonize medical devices but also significantly increases its tolerance to antibiotics, leading to chronic infections, particularly in immunocompromised patients. Clinically, biofilm formation in A. baumannii is associated with ventilator-associated pneumonia, bloodstream infections, and wound infections, posing a major challenge for treatment. Conventional antibiotics often fail to penetrate biofilms effectively, necessitating alternative therapeutic approaches such as quorum sensing inhibitors, biofilm-disrupting agents, and combination therapies. Understanding the genetic basis of biofilm formation is crucial for developing targeted interventions to mitigate A. baumannii-associated infections. Future research should focus on novel anti-biofilm strategies, including gene-targeting therapies and the use of biofilm-resistant biomaterials in medical devices. Addressing this issue is essential for improving patient outcomes and controlling the spread of multidrug-resistant A. baumannii in healthcare settings.
References
R. Thummeepak, P. Kongthai, U. Leungtongkam, and S. Sitthisak, "Distribution of virulence genes involved in biofilm formation in multi-drug resistant Acinetobacter baumannii clinical isolates," [PDF], 2016.
M. Nguyen and S. G. Joshi, "Carbapenem resistance in Acinetobacter baumannii, and their importance in hospital‐acquired infections: a scientific review," J. Appl. Microbiol., 2021.
Nithichanon, C. Kewcharoenwong, H. Da-Oh, S. Surajinda, A. Khongmee, S. Koosakunwat, et al., "Acinetobacter nosocomialis causes as severe disease as Acinetobacter baumannii in Northeast Thailand: underestimated role of A. nosocomialis in infection," Microbiol. Spectrum, vol. 10, no. 6, pp. e02836-22, 2022.
Ma and S. McClean, "Mapping global prevalence of Acinetobacter baumannii and recent vaccine development to tackle it," Vaccines, 2021.
M. K. Abban, E. A. Ayerakwa, L. Mosi, and A. Isawumi, "The burden of hospital acquired infections and antimicrobial resistance," Heliyon, 2023.
Adnan, Z. Mohammed Farhan, and O. A. Mohsein, "Understanding the link between diabetes mellitus and fatty liver disease: A narrative review," Int. J. Chem. Stud., vol. 12, no. 4, pp. 40–48, 2024.
Gedefie, W. Demsis, M. Ashagrie, Y. Kassa, M. Tesfaye, M. Tilahun, et al., "Acinetobacter baumannii biofilm formation and its role in disease pathogenesis: a review," Infect. Drug Resist., pp. 3711–3719, 2021.
M. Assefa and A. Amare, "Biofilm-associated multi-drug resistance in hospital-acquired infections: a review," Infect. Drug Resist., 2022.
S. Roy, G. Chowdhury, A. K. Mukhopadhyay, S. Dutta, and S. Basu, "Convergence of biofilm formation and antibiotic resistance in Acinetobacter baumannii infection," Front. Med., vol. 9, p. 793615, 2022.
Z. Li, Z. Ding, Y. Liu, X. Jin, J. Xie, T. Li, et al., "Phenotypic and genotypic characteristics of biofilm formation in clinical isolates of Acinetobacter baumannii," Infect. Drug Resist., pp. 2613–2624, 2021.
S. Martí, J. Rodríguez-Baño, M. Catel-Ferreira, T. Jouenne, J. Vila, H. Seifert, and E. Dé, "Biofilm formation at the solid-liquid and air-liquid interfaces by Acinetobacter species,"
F. P. Nocera, A. R. Attili, and L. De Martino, "Acinetobacter baumannii: Its clinical significance in human and veterinary medicine," Pathogens, 2021.
K. Rangel, T. P. G. Chagas, and S. G. De-Simone, "Acinetobacter baumannii infections in times of COVID-19 pandemic," Pathogens, 2021.
Valcek, C. Philippe, C. Whiteway, E. Robino, K. Nesporova, M. Bové, et al., "Phenotypic characterization and heterogeneity among modern clinical isolates of Acinetobacter baumannii," Microbiol. Spectrum, vol. 11, no. 1, p. e03061-22, 2023.
R. Dehbanipour and Z. Ghalavand, "Acinetobacter baumannii: Pathogenesis, virulence factors, novel therapeutic options and mechanisms of resistance to antimicrobial agents with emphasis on tigecycline," J. Clin. Pharm. Ther., vol. 47, no. 11, pp. 1875–1884, 2022.
Z. Q. Mohammed Hilo, A. Mahmood, and O. A. Mohsein, "Genomic insights into Staphylococcus aureus: Mechanisms of antibiotic resistance and virulence gene expression," Eur. J. Ecol. Biol. Agric., vol. 1, no. 5, pp. 29–48, 2024.
G. Mancuso, A. Midiri, E. Gerace, and C. Biondo, "Bacterial antibiotic resistance: the most critical pathogens," Pathogens, 2021.
G. K. Oyejobi, S. O. Olaniyan, N. A. Yusuf, D. A. Ojewande, M. J. Awopetu, G. O. Oyeniran, et al., "Acinetobacter baumannii: More ways to die," Microbiol. Res., vol. 261, p. 127069, 2022.
K. G. Dolma and W. M. MD, "Acinetobacter baumannii: An overview of emerging multidrug-resistant pathogen," Med. J. Malaysia, 2022.
Pompilio, D. Scribano, M. Sarshar, G. Di Bonaventura, A. T. Palamara, and C. Ambrosi, "Gram-negative bacteria holding together in a biofilm: the Acinetobacter baumannii way," Microorganisms, vol. 9, no. 7, p. 1353, 2021.
S. G. Mendes, S. I. Combo, T. Allain, S. Buret, and G. J. Da Silva, "Co-regulation of biofilm formation and antimicrobial resistance in Acinetobacter baumannii: from mechanisms to therapeutic strategies," Eur. J. Clin. Microbiol. Infect. Dis., vol. 42, no. 12, pp. 1405-1423, 2023.
N. N. Pathoor, P. S. Ganesh, and R. K. Gopal, "Microbiome interactions: Acinetobacter baumannii biofilms as a co-factor in oral cancer progression," World J. Microbiol. Biotechnol., vol. 40, no. 12, p. 398, 2024.
V. Kaushik, M. Tiwari, R. Joshi, and V. Tiwari, "Therapeutic strategies against potential antibiofilm targets of multidrug‐resistant Acinetobacter baumannii," J. Cell. Physiol., vol. 237, no. 4, pp. 2045-2063, 2022.
F. Khan, "Strategies for controlling biofilm-forming microbial pathogens on biotic and abiotic surfaces," Curr. Drug Targets, 2022.
E. Parrilli, M. L. Tutino, and G. Marino, "Biofilm as an adaptation strategy to extreme conditions," Rendiconti Lincei. Scienze Fisiche e Naturali, vol. 33, no. 3, pp. 527-536, 2022.
M. A. Ismail et al., "Exploring the genetic variability of Escherichia coli pathotypes in urinary tract infections: implications for diagnostics and treatment," Cent. Asian J. Med. Nat. Sci., vol. 6, no. 1, pp. 179-191, 2024.
Y. Farrokhi, Z. Neshati, P. Saniee, and A. Makhdoumi, "The potential of Bacillus and Enterococcus probiotic strains to combat Helicobacter pylori attachment to the biotic and abiotic surfaces," Int. Microbiol., 2023.
K. Upmanyu, R. Kumar, Q. M. Rizwanul Haque, and R. Singh, "Exploring the evolutionary and pathogenic role of Acinetobacter baumannii biofilm-associated protein (Bap) through in silico structural modeling," Arch. Microbiol., vol. 206, no. 6, p. 267, 2024.
E. Cihan and S. Turkyilmaz, "Investigation of biofilm formation, virulence genes and antibiotic resistance of Acinetobacter baumannii isolates obtained from clinical samples," Isr. J. Vet. Med., 2024.
H. Wang et al., "Transcriptome analysis revealed the role of capsular polysaccharides in desiccation tolerance of foodborne Staphylococcus aureus," Food Res. Int., vol. 159, p. 111602, 2022.
L. Zhao et al., "Novel berberine derivatives as adjuvants in the battle against Acinetobacter baumannii: A promising strategy for combating multi-drug resistance," Chinese Chem. Lett., vol. 35, no. 10, p. 109506, 2024.
S. Qassim Mohammad, Sarmad, A. Khazal Mohsen, and I. S. Jalil, "Assessing the prevalence of bacterial vaginosis among infertile women in Thi-Qar Province, Iraq," Infect. Epidemiol. Microbiol., vol. 10, no. 4, pp. 287-296, 2024.
K. Luo et al., "Revealing the mechanism of citral induced entry of Vibrio vulnificus into viable but not culturable (VBNC) state based on transcriptomics," Int. J. Food Microbiol., vol. 416, p. 110656, 2024.
P. Zhang et al., "Whole-genome sequencing and transcriptome-characterized mechanism of streptomycin resistance in Vibrio parahaemolyticus O10: K4," Infect. Genet. Evol., vol. 117, p. 105540, 2024.
J. L. Allen, "Multifaceted approach to understanding Acinetobacter baumannii biofilm formation and drug resistance," [Online]. Available: usf.edu, 2021.
N. A. Abdulmuttaleb, N. Azhar, M. Q. Mohammed, and O. A. Mohsein, "Exploring the connection between inflammatory cytokines, hypertension, and diabetes in angina patients," Cytokines, vol. 14, no. 15, p. 16, 2024.
N. Pathoor, A. Viswanathan, G. Wadhwa, and P. S. Ganesh, "Understanding the biofilm development of Acinetobacter baumannii and novel strategies to combat infection," APMIS, vol. 132, no. 5, pp. 317-335, 2024.
M. Marazzato et al., "Genetic diversity of antimicrobial resistance and key virulence features in two extensively drug-resistant Acinetobacter baumannii isolates," Int. J. Environ. Res. Public Health, vol. 19, no. 5, p. 2870, 2022.
R. Q. Taha et al., "Bacterial aetiologies of otitis media and their antimicrobial susceptibility in ear swab culture," IJBS, vol. 6, no. 1, pp. 94-99, 2024.
Q. Ababneh, S. Abu Laila, and Z. Jaradat, "Prevalence, genetic diversity, antibiotic resistance and biofilm formation of Acinetobacter baumannii isolated from urban environments," J. Appl. Microbiol., vol. 133, no. 6, pp. 3617-3633, 2022.
M. López-Martín, J. F. Dubern, M. R. Alexander, and P. Williams, "AbaM regulates quorum sensing, biofilm formation, and virulence in Acinetobacter baumannii," J. Bacteriol., vol. 203, no. 8, pp. 10-1128, 2021.
M. M. Islam, K. Kim, J. C. Lee, and M. Shin, "LeuO, a LysR-type transcriptional regulator, is involved in biofilm formation and virulence of Acinetobacter baumannii," Front. Cell. Infect. Microbiol., vol. 11, p. 738706, 2021.
O. A. Abd El-Rahman, F. Rasslan, S. S. Hassan, H. M. Ashour, and R. Wasfi, "The RND efflux pump gene expression in the biofilm formation of Acinetobacter baumannii," Antibiotics, vol. 12, no. 2, p. 419, 2023.
X. Sun and J. Xiang, "Mechanism underlying the role of LuxR family transcriptional regulator abaR in biofilm formation by Acinetobacter baumannii," Curr. Microbiol., 2021.
E. F. Haney, M. J. Trimble, J. T. Cheng, Q. Vallé, and R. E. W. Hancock, "Critical assessment of methods to quantify biofilm growth and evaluate antibiofilm activity of host defence peptides," 2018.
M. Alamri, A. A. Alsultan, A. M. Ansari, and A. M. Alnimr, "Biofilm-formation in clonally unrelated multidrug-resistant Acinetobacter baumannii isolates," 2020.
S. Pugazhendhi, F. Wei, M. Hughes, and M. Coathup, "Bacterial adhesion, virulence, and biofilm formation," in Musculoskeletal Infection, Cham: Springer International Publishing, 2022, pp. 19-64.
Abdulhussien, Z. M. Farhan, and O. A. Mohsein, "The clinico-pathological role of horizontal gene transfer in the ability of Pseudomonas aeruginosa to cause disease in lung tissue," Eur. J. Med. Health Res., vol. 3, no. 1, pp. 27-34, 2025.
D. Wang, L. Wang, Q. Liu, and Y. Zhao, "Virulence factors in biofilm formation and therapeutic strategies for Staphylococcus aureus: A review," Animals and Zoonoses, 2024.
V. P. P. Alonso, J. G. Lemos, and M. D. S. do Nascimento, "Yeast biofilms on abiotic surfaces: Adhesion factors and control methods," Int. J. Food Microbiol., vol. 400, p. 110265, 2023.
N. Janež, B. Škrlj, M. Sterniša, A. Klančnik, and J. Sabotič, "The role of the Listeria monocytogenes surfactome in biofilm formation," Microb. Biotechnol., vol. 14, no. 4, pp. 1269-1281, 2021. [Online]. Available: wiley.com.
G. J. Jeong, F. Khan, N. Tabassum, and Y. M. Kim, "Natural and synthetic molecules with potential to enhance biofilm formation and virulence properties in Pseudomonas aeruginosa," Crit. Rev. Microbiol., vol. 50, no. 5, pp. 830-858, 2024.
J. J. Harrison, H. Ceri, J. Yerly, C. A. Stremick, Y. Hu, R. Martinuzzi, and R. J. Turner, "The use of microscopy and three-dimensional visualization to evaluate the structure of microbial biofilms cultivated in the Calgary Biofilm Device," 2006.
D. K. Bhardwaj, N. K. Taneja, D. P. Shivaprasad, A. Chakotiya, P. Patel, P. Taneja, et al., "Phenotypic and genotypic characterization of biofilm forming, antimicrobial resistant, pathogenic Escherichia coli isolated from Indian dairy and meat products," Int. J. Food Microbiol., vol. 336, p. 108899, 2021. [Online]. Available: researchgate.net.
Silva, V. Silva, M. López, B. Rojo-Bezares, J. A. Carvalho, A. P. Castro, et al., "Antimicrobial resistance, genetic lineages, and biofilm formation in Pseudomonas aeruginosa isolated from human infections: an emerging one health concern," Antibiotics, vol. 12, no. 8, p. 1248, 2023. [Online]. Available: mdpi.com.
E. M. Mlugu, J. A. Mohamedi, R. Z. Sangeda, and K. D. Mwambete, "Prevalence of urinary tract infection and antimicrobial resistance patterns of uropathogens with biofilm forming capacity among outpatients in Morogoro, Tanzania: A cross-sectional study," BMC Infect. Dis., vol. 23, no. 1, p. 660, 2023. [Online]. Available: springer.com.
V. Folliero, G. Franci, F. Dell’Annunziata, R. Giugliano, F. Foglia, R. Sperlongano, et al., "Evaluation of antibiotic resistance and biofilm production among clinical strain isolated from medical devices," Int. J. Microbiol., 2021, p. 9033278.
S. Barathi, K. N. Aruljothi, C. Karthik, I. A. Padikasan, and V. Ashokkumar, "Biofilm mediated decolorization and degradation of reactive red 170 dye by the bacterial consortium isolated from the dyeing industry wastewater sediments," Chemosphere, vol. 286, p. 131914, 2022.
M. E. Kuc, S. Azerrad, O. Menashe, and E. Kurzbaum, "Efficient biodegradation of phenol at high concentrations by Acinetobacter biofilm at extremely short hydraulic retention times," J. Water Process Eng., vol. 47, p. 102781, 2022.
Elbehiry, E. Marzouk, I. M. Moussa, T. M. Dawoud, A. S. Mubarak, D. Al-Sarar, et al., "Acinetobacter baumannii as a community foodborne pathogen: Peptide mass fingerprinting analysis, genotypic of biofilm formation and phenotypic pattern of antimicrobial resistance," Saudi J. Biol. Sci., vol. 28, no. 1, pp. 1158-1166, 2021.
Syed, M. T. Zeyad, M. Shahid, A. M. Elgorban, M. M. Alkhulaifi, and I. A. Ansari, "Heavy metals induced modulations in growth, physiology, cellular viability, and biofilm formation of an identified bacterial isolate," ACS Omega, vol. 6, no. 38, pp. 25076–25088, 2021.
Neuman, L. Shvartser, S. Teppler, Y. Friedman, J. J. Levine, I. Kagan, et al., "A machine-learning model for prediction of Acinetobacter baumannii hospital acquired infection," PloS One, vol. 19, no. 12, p. e0311576, 2024.
D. Alrahmany, A. F. Omar, G. Harb, W. S. El Nekidy, and I. M. Ghazi, "Acinetobacter baumannii infections in hospitalized patients, treatment outcomes," Antibiotics, vol. 10, no. 6, p. 630, 2021.
S. J. Mun, S. H. Kim, H. T. Kim, C. Moon, and Y. M. Wi, "Epidemiology of bloodstream infection contributing to mortality: The difference between community-acquired, healthcare-associated, and hospital-acquired infections," BMC Infect. Dis., 2022.
O. Nassar, S. E. Desouky, G. M. El-Sherbiny, and M. Abu-Elghait, "Correlation between phenotypic virulence traits and antibiotic resistance in Pseudomonas aeruginosa clinical isolates," Microbial Pathogenesis, vol. 162, p. 105339, 2022.
J.-P. V. Jean-Pierre, A. Boudet, P. Sorlin, Q. Menetrey, R. Chiron, J. P. Lavigne, and H. Marchandin, "Biofilm formation by Staphylococcus aureus in the specific context of cystic fibrosis," Int. J. Mol. Sci., vol. 24, no. 1, p. 597, 2022.
V. Charron‐Lamoureux, S. Lebel‐Beaucage, M. Pomerleau, and P. B. Beauregard, "Rooting for success: Evolutionary enhancement of Bacillus for superior plant colonization," Microbial Biotechnol., vol. 17, no. 9, p. e70001, 2024.
T. Ranković, I. Nikolić, T. Berić, T. Popović, J. Lozo, O. Medić, and S. Stanković, "Genome analysis of two Pseudomonas syringae pv. Aptata strains with different virulence capacity isolated from sugar beet: Features of successful pathogenicity in the Phyllosphere microbiome," Microbiology Spectrum, vol. 11, no. 2, p. e03598-22, 2023.
C. Rossi, F. Ahmad, and M. Giambiagi-deMarval, "An updated review on nosocomial infections, antimicrobial resistance, virulence, genetic traits, and strategies for combating this emerging opportunistic pathogen," Microbiol. Res., 2024.
X. Wang, K. Gao, B. Pan, B. Wang, Y. Song, and W. Guo, "The virulence trait and genotype distribution amongst the Pseudomonas aeruginosa clinical strains," BMC Microbiol., vol. 25, p. 82, 2025.
M. M. Lucidi, D. Visaggio, A. Migliaccio, G. Capecchi, P. Visca, F. Imperi, and R. Zarrilli, "Pathogenicity and virulence of Acinetobacter baumannii: Factors contributing to the fitness in healthcare settings and the infected host," Virulence, vol. 15, no. 1, p. 2289769, 2024.
S. Truşcă, I. Gheorghe-Barbu, M. Manea, E. Ianculescu, I. C. Barbu, L. G. Măruțescu, et al., "Snapshot of phenotypic and molecular virulence and resistance profiles in multidrug-resistant strains isolated in a tertiary hospital in Romania," Pathogens, vol. 12, no. 4, p. 609, 2023.
Upmanyu, Q. M. R. Haq, and R. Singh, "Factors mediating Acinetobacter baumannii biofilm formation: Opportunities for developing therapeutics," Curr. Res. Microbial Sci., 2022.
J. Sanchez, K. Mende, L. Beckius, S. Akers, R. Romano, C. Wenke, and K. Murray, "Biofilm formation by clinical isolates and the implications in chronic infections," 2013.
Pugazhendhi, S. Vasantharaj, S. Sathiyavimal, R. K. Raja, I. Karuppusamy, M. Narayanan, et al., "Organic and inorganic nanomaterial coatings for the prevention of microbial growth and infections on biotic and abiotic surfaces," Surf. Coat. Technol., vol. 425, p. 127739, 2021. [Online]. Available: [HTML]
N. Bouhrour, P. H. Nibbering, and F. Bendali, "Medical device-associated biofilm infections and multidrug-resistant pathogens," Pathogens, 2024.
Mishra, A. Aggarwal, and F. Khan, "Medical device-associated infections caused by biofilm-forming microbial pathogens and controlling strategies," Antibiotics, 2024.
Q. Ababneh, S. Abulaila, and Z. Jaradat, "Isolation of extensively drug resistant Acinetobacter baumannii from environmental surfaces inside intensive care units," Am. J. Infect. Control, 2022.
M. G. Donadu, V. Mazzarello, P. Cappuccinelli, S. Zanetti, M. Madléna, Á. L. Nagy, et al., "Relationship between the biofilm-forming capacity and antimicrobial resistance in clinical Acinetobacter baumannii isolates: Results from a laboratory-based in vitro study," Microorganisms, vol. 9, no. 11, p. 2384, 2021.
M. M. Al-Shamiri, S. Zhang, P. Mi, Y. Liu, M. Xun, E. Yang, et al., "Phenotypic and genotypic characteristics of Acinetobacter baumannii enrolled in the relationship among antibiotic resistance, biofilm formation and motility," Microbial Pathogenesis, vol. 155, p. 104922, 2021.
Upmanyu, Q. M. R. Mohd. Rizwanul Haq, and R. Singh, "Factors mediating Acinetobacter baumannii biofilm formation: Opportunities for developing therapeutics," ncbi.nlm.nih.gov, 2022.
Javadi, "Acinetobacter baumannii in the Healthcare Facility Setting," Avicenna Journal of Clinical Microbiology and Infection, 2024. [Online]. Available: umsha.ac.ir.
Y. Tan, J. Su, M. Fu, H. Zhang, and H. Zeng, "Recent Advances in Phage-Based Therapeutics for Multi-Drug Resistant Acinetobacter baumannii," Bioengineering, 2022.
Y. Zhang, Y. Lin, S. Galgano, J. Houdijk, W. Xie, Y. Jin, and T. Li, "Recent progress in phage therapy to modulate multidrug-resistant Acinetobacter baumannii, including in human and poultry," Antibiotics, vol. 11, no. 10, pp. 1406, 2022.
S. Ibrahim, N. Al-Saryi, I. M. S. Al-Kadmy, and S. N. Aziz, "Multidrug-resistant Acinetobacter baumannii as an emerging concern in hospitals," Molecular Biology Reports, 2021.
T. Umemura, H. Kato, M. Hagihara, J. Hirai, Y. Yamagishi, and H. Mikamo, "Efficacy of combination therapies for the treatment of multi-drug resistant Gram-negative bacterial infections based on meta-analyses," Antibiotics, vol. 11, no. 4, p. 524, 2022.
Rabin, S. A. W. M. G. M. R. J. M. B. H., "Biofilm formation mechanisms and targets for developing antibiofilm agents," Future Medicinal Chemistry, vol. 7, no. 4, pp. 493-512, 2015.
S. T. Asma, "An overview of biofilm formation–combating strategies and mechanisms of action of antibiofilm agents," Life, vol. 12, no. 8, p. 1110, 2022.
R. B. Mokhtari, et al., "Combination therapy in combating cancer," Oncotarget, vol. 8, no. 23, pp. 38022, 2017.
Postiglione, A. Chiaviello, and G. Palumbo, "Enhancing photodynamic therapy efficacy by combination therapy: dated, current and oncoming strategies," Cancers, vol. 3, no. 2, pp. 2597-2629, 2011.
Copyright (c) 2025 Qabas Neamah Hadi, Dhuhah Hayder Abdul-Jawad, Alia Essa Bashbosh, Osama A.Mohsein
This work is licensed under a Creative Commons Attribution 4.0 International License.
