Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Uncovering the mechanisms of Acinetobacter baumannii virulence

Key Points

  • Acinetobacter baumannii is an opportunistic human pathogen that predominantly causes health-care-associated infections.

  • Many members of the genus Acinetobacter, including Acinetobacter nosocomialis, Acinetobacter pittii, Acinetobacter dijkshoorniae and Acinetobacter seifertii, are also human pathogens and increasingly identified as the cause of infections.

  • A. baumannii is rapidly developing resistance mechanisms to antibiotics.

  • The ability of A. baumannii to withstand desiccation and to form biofilms promotes its success as a nosocomial pathogen.

  • Fundamental virulence factors, such as surface adhesins, glycoconjugates and secretion systems, directly contribute to the pathogenesis of A. baumannii.

Abstract

Acinetobacter baumannii is a nosocomial pathogen that causes ventilator-associated as well as bloodstream infections in critically ill patients, and the spread of multidrug-resistant Acinetobacter strains is cause for concern. Much of the success of A. baumannii can be directly attributed to its plastic genome, which rapidly mutates when faced with adversity and stress. However, fundamental virulence mechanisms beyond canonical drug resistance were recently uncovered that enable A. baumannii and, to a limited extent, other medically relevant Acinetobacter species to successfully thrive in the health-care environment. In this Review, we explore the molecular features that promote environmental persistence, including desiccation resistance, biofilm formation and motility, and we discuss the most recently identified virulence factors, such as secretion systems, surface glycoconjugates and micronutrient acquisition systems that collectively enable these pathogens to successfully infect their hosts.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Protein secretion and export in Acinetobacter baumannii.
Figure 2: Acinetobacter baumannii surface-exposed glycoconjugates.
Figure 3: Colistin resistance mechanisms of Acinetobacter baumannii.

References

  1. Giammanco, A., Cala, C., Fasciana, T. & Dowzicky, M. J. Global assessment of the activity of tigecycline against multidrug-resistant Gram-negative pathogens between 2004 and 2014 as part of the tigecycline evaluation and surveillance trial. mSphere 2, e00310-16 (2017). This excellent study demonstrates the global rates of drug resistance of A. baumannii compared with other prevalent Gram-negative bacteria.

    PubMed Central  PubMed  Google Scholar 

  2. Rolain, J. M. et al. Real-time sequencing to decipher the molecular mechanism of resistance of a clinical pan-drug-resistant Acinetobacter baumannii isolate from Marseille, France. Antimicrob. Agents Chemother. 57, 592–596 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Magill, S. S. et al. Multistate point-prevalence survey of health care-associated infections. N. Engl. J. Med. 370, 1198–1208 (2014).

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Lob, S. H., Hoban, D. J., Sahm, D. F. & Badal, R. E. Regional differences and trends in antimicrobial susceptibility of Acinetobacter baumannii. Int. J. Antimicrob. Agents 47, 317–323 (2016).

    CAS  PubMed  Google Scholar 

  5. Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013 (CDC, 2013).

  6. World Health Organization. Global priority list of antibiotic-resistant bacteria to guide researach, discovery and development of new antibiotics. WHO http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf?ua=1 (2017).

  7. Mari-Almirall, M. et al. MALDI-TOF/MS identification of species from the Acinetobacter baumannii (Ab) group revisited: inclusion of the novel A. seifertii and A. dijkshoorniae species. Clin. Microbiol. Infect. 23, 210.e1–210.e9 (2017).

    CAS  Google Scholar 

  8. Sievert, D. M. et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009–2010. Infect. Control Hosp. Epidemiol. 34, 1–14 (2013).

    PubMed  Google Scholar 

  9. Weiner, L. M. et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infect. Control Hosp. Epidemiol. 37, 1288–1301 (2016).

    PubMed  Google Scholar 

  10. Dexter, C., Murray, G. L., Paulsen, I. T. & Peleg, A. Y. Community-acquired Acinetobacter baumannii: clinical characteristics, epidemiology and pathogenesis. Expert Rev. Anti Infect. Ther. 13, 567–573 (2015).

    CAS  PubMed  Google Scholar 

  11. Touchon, M. et al. The genomic diversification of the whole Acinetobacter genus: origins, mechanisms, and consequences. Genome Biol. Evol. 6, 2866–2882 (2014).

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Bouvet, P. J. M. & Grimont, P. A. D. Taxonomy of the genus Acinetobacter with the recognition of Acinetobacter baumannii sp. nov., Acinetobacter haemolyticus sp. nov., Acinetobacter johnsonii sp. nov., and Acinetobacter junii sp. nov. and emended descriptions of Acinetobacter calcoaceticus and Acinetobacter lwoffii. Int. J. Syst. Bacteriol. 36, 228–240 (1986).

    CAS  Google Scholar 

  13. Nemec, A. et al. Genotypic and phenotypic characterization of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex with the proposal of Acinetobacter pittii sp. nov. (formerly Acinetobacter genomic species 3) and Acinetobacter nosocomialis sp. nov. (formerly Acinetobacter genomic species 13TU). Res. Microbiol. 162, 393–404 (2011).

    CAS  PubMed  Google Scholar 

  14. Nemec, A. et al. Acinetobacter seifertii sp. nov., a member of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex isolated from human clinical specimens. Int. J. Syst. Evol. Microbiol. 65, 934–942 (2015).

    CAS  PubMed  Google Scholar 

  15. Cosgaya, C. et al. Acinetobacter dijkshoorniae sp. nov., a member of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex mainly recovered from clinical samples in different countries. Int. J. Syst. Evol. Microbiol. 66, 4105–4111 (2016).

    CAS  PubMed  Google Scholar 

  16. Espinal, P., Seifert, H., Dijkshoorn, L., Vila, J. & Roca, I. Rapid and accurate identification of genomic species from the Acinetobacter baumannii (Ab) group by MALDI-TOF MS. Clin. Microbiol. Infect. 18, 1097–1103 (2012).

    CAS  PubMed  Google Scholar 

  17. Chusri, S. et al. Clinical outcomes of hospital-acquired infection with Acinetobacter nosocomialis and Acinetobacter pittii. Antimicrob. Agents Chemother. 58, 4172–4179 (2014).

    PubMed Central  PubMed  Google Scholar 

  18. Wong, D. et al. Clinical and pathophysiological overview of Acinetobacter infections: a century of challenges. Clin. Microbiol. Rev. 30, 409–447 (2017). This excellent review article comprehensively covers many of the clinical features of Acinetobacter spp. infections as well as virulence mechanisms and animal models.

    CAS  PubMed  Google Scholar 

  19. Roca, I., Espinal, P., Vila-Farres, X. & Vila, J. The Acinetobacter baumannii oxymoron: commensal hospital dweller turned pan-drug-resistant menace. Front. Microbiol. 3, 148 (2012).

    PubMed Central  PubMed  Google Scholar 

  20. Giannouli, M. et al. Virulence-related traits of epidemic Acinetobacter baumannii strains belonging to the international clonal lineages I-III and to the emerging genotypes ST25 and ST78. BMC Infect. Dis. 13, 282 (2013).

    PubMed Central  PubMed  Google Scholar 

  21. Antunes, L. C., Imperi, F., Carattoli, A. & Visca, P. Deciphering the multifactorial nature of Acinetobacter baumannii pathogenicity. PLoS ONE 6, e22674 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Ophir, T. & Gutnick, D. L. A role for exopolysaccharides in the protection of microorganisms from desiccation. Appl. Environ. Microbiol. 60, 740–745 (1994).

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Scott, N. E. et al. Diversity within the O-linked protein glycosylation systems of Acinetobacter species. Mol. Cell Proteom. 13, 2354–2370 (2014).

    CAS  Google Scholar 

  24. Espinal, P., Marti, S. & Vila, J. Effect of biofilm formation on the survival of Acinetobacter baumannii on dry surfaces. J. Hosp. Infect. 80, 56–60 (2012).

    CAS  PubMed  Google Scholar 

  25. Boll, J. M. et al. Reinforcing lipid A acylation on the cell surface of Acinetobacter baumannii promotes cationic antimicrobial peptide resistance and desiccation survival. mBio 6, e00478-15 (2015).

    PubMed Central  PubMed  Google Scholar 

  26. Bravo, Z. et al. The long-term survival of Acinetobacter baumannii ATCC 19606T under nutrient-deprived conditions does not require the entry into the viable but non-culturable state. Arch. Microbiol. 198, 399–407 (2016).

    CAS  PubMed  Google Scholar 

  27. Potts, M. Desiccation tolerance of prokaryotes. Microbiol. Rev. 58, 755–805 (1994).

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Aranda, J. et al. Acinetobacter baumannii RecA protein in repair of DNA damage, antimicrobial resistance, general stress response, and virulence. J. Bacteriol. 193, 3740–3747 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Norton, M. D., Spilkia, A. J. & Godoy, V. G. Antibiotic resistance acquired through a DNA damage-inducible response in Acinetobacter baumannii. J. Bacteriol. 195, 1335–1345 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Gayoso, C. M. et al. Molecular mechanisms involved in the response to desiccation stress and persistence in Acinetobacter baumannii. J. Proteome Res. 13, 460–476 (2014).

    CAS  PubMed  Google Scholar 

  31. Derecho, I., McCoy, K. B., Vaishampayan, P., Venkateswaran, K. & Mogul, R. Characterization of hydrogen peroxide-resistant Acinetobacter species isolated during the Mars Phoenix spacecraft assembly. Astrobiology 14, 837–847 (2014).

    CAS  PubMed  Google Scholar 

  32. Nemec, A. et al. Acinetobacter beijerinckii sp. nov. and Acinetobacter gyllenbergii sp. nov., haemolytic organisms isolated from humans. Int. J. Syst. Evol. Microbiol. 59, 118–124 (2009).

    CAS  PubMed  Google Scholar 

  33. Wright, M. S., Mountain, S., Beeri, K. & Adams, M. D. Assessment of insertion sequence mobilization as an adaptive response to oxidative stress in Acinetobacter baumannii using IS-Seq. J. Bacteriol. 199, e00833-16 (2017). This paper demonstrates how plastic the A. baumannii genome can be when faced with stress, particularly oxidative stress.

    PubMed Central  PubMed  Google Scholar 

  34. Hassan, K. A. et al. Transcriptomic and biochemical analyses identify a family of chlorhexidine efflux proteins. Proc. Natl Acad. Sci. USA 110, 20254–20259 (2013).

    CAS  PubMed  Google Scholar 

  35. Nwugo, C. C. et al. Effect of ethanol on differential protein production and expression of potential virulence functions in the opportunistic pathogen Acinetobacter baumannii. PLoS ONE 7, e51936 (2012).

    PubMed Central  PubMed  Google Scholar 

  36. Camarena, L., Bruno, V., Euskirchen, G., Poggio, S. & Snyder, M. Molecular mechanisms of ethanol-induced pathogenesis revealed by RNA-sequencing. PLoS Pathog. 6, e1000834 (2010).

    PubMed Central  PubMed  Google Scholar 

  37. Smith, M. G., Des Etages, S. G. & Snyder, M. Microbial synergy via an ethanol-triggered pathway. Mol. Cell. Biol. 24, 3874–3884 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Asplund, M. B., Coelho, C., Cordero, R. J. & Martinez, L. R. Alcohol impairs J774.16 macrophage-like cell antimicrobial functions in Acinetobacter baumannii infection. Virulence 4, 467–472 (2013).

    PubMed Central  PubMed  Google Scholar 

  39. Thompson, M. G. et al. Validation of a novel murine wound model of Acinetobacter baumannii infection. Antimicrob. Agents Chemother. 58, 1332–1342 (2014).

    PubMed Central  PubMed  Google Scholar 

  40. Greene, C., Wu, J., Rickard, A. H. & Xi, C. Evaluation of the ability of Acinetobacter baumannii to form biofilms on six different biomedical relevant surfaces. Lett. Appl. Microbiol. 63, 233–239 (2016).

    CAS  PubMed  Google Scholar 

  41. Greene, C., Vadlamudi, G., Newton, D., Foxman, B. & Xi, C. The influence of biofilm formation and multidrug resistance on environmental survival of clinical and environmental isolates of Acinetobacter baumannii. Am. J. Infect. Control 44, e65–e71 (2016).

    CAS  PubMed  Google Scholar 

  42. Tomaras, A. P., Flagler, M. J., Dorsey, C. W., Gaddy, J. A. & Actis, L. A. Characterization of a two-component regulatory system from Acinetobacter baumannii that controls biofilm formation and cellular morphology. Microbiology 154, 3398–3409 (2008).

    CAS  PubMed  Google Scholar 

  43. Tomaras, A. P., Dorsey, C. W., Edelmann, R. E. & Actis, L. A. Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. Microbiology 149, 3473–3484 (2003).

    CAS  PubMed  Google Scholar 

  44. de Breij, A. et al. CsuA/BABCDE-dependent pili are not involved in the adherence of Acinetobacter baumannii ATCC19606T to human airway epithelial cells and their inflammatory response. Res. Microbiol. 160, 213–218 (2009).

    CAS  PubMed  Google Scholar 

  45. Wright, M. S., Iovleva, A., Jacobs, M. R., Bonomo, R. A. & Adams, M. D. Genome dynamics of multidrug-resistant Acinetobacter baumannii during infection and treatment. Genome Med. 8, 26 (2016).

    PubMed Central  PubMed  Google Scholar 

  46. Cerqueira, G. M. et al. A global virulence regulator in Acinetobacter baumannii and its control of the phenylacetic acid catabolic pathway. J. Infect. Dis. 210, 46–55 (2014).

    CAS  PubMed  Google Scholar 

  47. Moon, K. H., Weber, B. S. & Feldman, M. F. Subinhibitory concentrations of trimethoprim and sulfamethoxazole prevent biofilm formation by Acinetobacter baumannii through inhibition of Csu pili expression. Antimicrob. Agents Chemother. 61, e00778-17 (2017).

    PubMed Central  PubMed  Google Scholar 

  48. Marti, S. et al. Growth of Acinetobacter baumannii in pellicle enhanced the expression of potential virulence factors. PLoS ONE 6, e26030 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Eijkelkamp, B. A., Stroeher, U. H., Hassan, K. A., Paulsen, I. T. & Brown, M. H. Comparative analysis of surface-exposed virulence factors of Acinetobacter baumannii. BMC Genomics 15, 1020 (2014).

    PubMed Central  PubMed  Google Scholar 

  50. Loehfelm, T. W., Luke, N. R. & Campagnari, A. A. Identification and characterization of an Acinetobacter baumannii biofilm-associated protein. J. Bacteriol. 190, 1036–1044 (2008).

    CAS  PubMed  Google Scholar 

  51. Cucarella, C. et al. Bap, a Staphylococcus aureus surface protein involved in biofilm formation. J. Bacteriol. 183, 2888–2896 (2001).

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Harding, C. M. et al. Pathogenic Acinetobacter species have a functional type I secretion system and contact-dependent inhibition systems. J. Biol. Chem. 292, 9075–9087 (2017).

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Goh, H. M. et al. Molecular analysis of the Acinetobacter baumannii biofilm-associated protein. Appl. Environ. Microbiol. 79, 6535–6543 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  54. De Gregorio, E. et al. Biofilm-associated proteins: news from Acinetobacter. BMC Genomics 16, 933 (2015).

    PubMed Central  PubMed  Google Scholar 

  55. Satchell, K. J. Structure and function of MARTX toxins and other large repetitive RTX proteins. Annu. Rev. Microbiol. 65, 71–90 (2011).

    CAS  PubMed  Google Scholar 

  56. Choi, A. H., Slamti, L., Avci, F. Y., Pier, G. B. & Maira-Litran, T. The pgaABCD locus of Acinetobacter baumannii encodes the production of poly-β-1-6-N-acetylglucosamine, which is critical for biofilm formation. J. Bacteriol. 191, 5953–5963 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Bentancor, L. V., O'Malley, J. M., Bozkurt-Guzel, C., Pier, G. B. & Maira-Litran, T. Poly-N-acetyl-β-(1–6)-glucosamine is a target for protective immunity against Acinetobacter baumannii infections. Infect. Immun. 80, 651–656 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Russo, T. A. et al. The K1 capsular polysaccharide of Acinetobacter baumannii strain 307–0294 is a major virulence factor. Infect. Immun. 78, 3993–4000 (2010). This is the first paper to describe the role of capsular polysaccharide in A. baumannii virulence.

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Iwashkiw, J. A. et al. Identification of a general O-linked protein glycosylation system in Acinetobacter baumannii and its role in virulence and biofilm formation. PLoS Pathog. 8, e1002758 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Bentancor, L. V., Camacho-Peiro, A., Bozkurt-Guzel, C., Pier, G. B. & Maira-Litran, T. Identification of Ata, a multifunctional trimeric autotransporter of Acinetobacter baumannii. J. Bacteriol. 194, 3950–3960 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Eijkelkamp, B. A. et al. H-NS plays a role in expression of Acinetobacter baumannii virulence features. Infect. Immun. 81, 2574–2583 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Perez-Varela, M. et al. Mutants in the β-subunit of the RNA polymerase impairing the surface-associated motility and virulence of Acinetobacter baumannii. Infect. Immun. 85, e00327-17 (2017).

    PubMed Central  PubMed  Google Scholar 

  63. Vijayakumar, S. et al. Biofilm formation and motility depend on the nature of the Acinetobacter baumannii clinical isolates. Front. Public Health 4, 105 (2016).

    PubMed Central  PubMed  Google Scholar 

  64. Eijkelkamp, B. A. et al. Adherence and motility characteristics of clinical Acinetobacter baumannii isolates. FEMS Microbiol. Lett. 323, 44–51 (2011).

    CAS  PubMed  Google Scholar 

  65. Wilharm, G., Piesker, J., Laue, M. & Skiebe, E. DNA uptake by the nosocomial pathogen Acinetobacter baumannii occurs during movement along wet surfaces. J. Bacteriol. 195, 4146–4153 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Harding, C. M. et al. Acinetobacter baumannii strain M2 produces type IV pili which play a role in natural transformation and twitching motility but not surface-associated motility. mBio 4, e00360-13 (2013).

    PubMed Central  PubMed  Google Scholar 

  67. Jacobs, A. C. et al. Characterization of the Acinetobacter baumannii growth phase-dependent and serum responsive transcriptomes. FEMS Immunol. Med. Microbiol. 64, 403–412 (2012).

    CAS  PubMed  Google Scholar 

  68. Piepenbrink, K. H. et al. Structural diversity in the type IV pili of multidrug-resistant Acinetobacter. J. Biol. Chem. 291, 22924–22935 (2016).

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Henrichsen, J. Not gliding but twitching motility of Acinetobacter calcoaceticus. J. Clin. Pathol. 37, 102–103 (1984).

    CAS  PubMed Central  PubMed  Google Scholar 

  70. Clemmer, K. M., Bonomo, R. A. & Rather, P. N. Genetic analysis of surface motility in Acinetobacter baumannii. Microbiology 157, 2534–2544 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Kearns, D. B. A field guide to bacterial swarming motility. Nat. Rev. Microbiol. 8, 634–644 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Skiebe, E. et al. Surface-associated motility, a common trait of clinical isolates of Acinetobacter baumannii, depends on 1,3-diaminopropane. Int. J. Med. Microbiol. 302, 117–128 (2012).

    CAS  PubMed  Google Scholar 

  73. McQueary, C. N. et al. Extracellular stress and lipopolysaccharide modulate Acinetobacter baumannii surface-associated motility. J. Microbiol. 50, 434–443 (2012).

    CAS  PubMed  Google Scholar 

  74. Mussi, M. A. et al. The opportunistic human pathogen Acinetobacter baumannii senses and responds to light. J. Bacteriol. 192, 6336–6345 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Tipton, K. A., Dimitrova, D. & Rather, P. N. Phase-variable control of multiple phenotypes in Acinetobacter baumannii strain AB5075. J. Bacteriol. 197, 2593–2599 (2015).

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Tipton, K. A. & Rather, P. N. An ompR-envZ two-component system ortholog regulates phase variation, osmotic tolerance, motility, and virulence in Acinetobacter baumannii strain AB5075. J. Bacteriol. 199, e00705-16 (2016).

    Google Scholar 

  77. Garcia-Quintanilla, M., Pulido, M. R., Lopez-Rojas, R., Pachon, J. & McConnell, M. J. Emerging therapies for multidrug resistant Acinetobacter baumannii. Trends Microbiol. 21, 157–163 (2013).

    CAS  PubMed  Google Scholar 

  78. Peleg, A. Y. & Hooper, D. C. Hospital-acquired infections due to Gram-negative bacteria. N. Engl. J. Med. 362, 1804–1813 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Adams, M. D. et al. Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicrob. Agents Chemother. 53, 3628–3634 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Beceiro, A. et al. Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the pmrAB two-component regulatory system. Antimicrob. Agents Chemother. 55, 3370–3379 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Beceiro, A. et al. Biological cost of different mechanisms of colistin resistance and their impact on virulence in Acinetobacter baumannii. Antimicrob. Agents Chemother. 58, 518–526 (2014).

    PubMed Central  PubMed  Google Scholar 

  82. Pelletier, M. R. et al. Unique structural modifications are present in the lipopolysaccharide from colistin-resistant strains of Acinetobacter baumannii. Antimicrob. Agents Chemother. 57, 4831–4840 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Moffatt, J. H. et al. Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production. Antimicrob. Agents Chemother. 54, 4971–4977 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Boll, J. M. et al. A penicillin-binding protein inhibits selection of colistin-resistant, lipooligosaccharide-deficient Acinetobacter baumannii. Proc. Natl Acad. Sci. USA 113, E6228–E6237, (2016). This paper describes how A. baumannii can survive without LOS.

    CAS  PubMed  Google Scholar 

  85. Henry, R. et al. Colistin-resistant, lipopolysaccharide-deficient Acinetobacter baumannii responds to lipopolysaccharide loss through increased expression of genes involved in the synthesis and transport of lipoproteins, phospholipids, and poly-β-1,6-N-acetylglucosamine. Antimicrob. Agents Chemother. 56, 59–69 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Lees-Miller, R. G. et al. A common pathway for O-linked protein-glycosylation and synthesis of capsule in Acinetobacter baumannii. Mol. Microbiol. 89, 816–830 (2013).

    CAS  PubMed  Google Scholar 

  87. Harding, C. M. et al. Acinetobacter strains carry two functional oligosaccharyltransferases, one devoted exclusively to type IV pilin, and the other one dedicated to O-glycosylation of multiple proteins. Mol. Microbiol. 96, 1023–1041 (2015).

    CAS  PubMed  Google Scholar 

  88. Geisinger, E. & Isberg, R. R. Antibiotic modulation of capsular exopolysaccharide and virulence in Acinetobacter baumannii. PLoS Pathog. 11, e1004691 (2015).

    PubMed Central  PubMed  Google Scholar 

  89. Wang, N., Ozer, E. A., Mandel, M. J. & Hauser, A. R. Genome-wide identification of Acinetobacter baumannii genes necessary for persistence in the lung. mBio 5, e01163-14 (2014).

    PubMed Central  PubMed  Google Scholar 

  90. Subashchandrabose, S. et al. Acinetobacter baumannii genes required for bacterial survival during bloodstream infection. mSphere http://dx.doi.org/10.1128/mSphere.00013-15 (2016).

  91. Gebhardt, M. J. et al. Joint transcriptional control of virulence and resistance to antibiotic and environmental stress in Acinetobacter baumannii. mBio 6, e01660-15 (2015).

    PubMed Central  PubMed  Google Scholar 

  92. Antunes, L. C., Imperi, F., Towner, K. J. & Visca, P. Genome-assisted identification of putative iron-utilization genes in Acinetobacter baumannii and their distribution among a genotypically diverse collection of clinical isolates. Res. Microbiol. 162, 279–284 (2011).

    CAS  PubMed  Google Scholar 

  93. Shapiro, J. A. & Wencewicz, T. A. Acinetobactin isomerization enables adaptive iron acquisition in Acinetobacter baumannii through pH-triggered siderophore swapping. ACS Infect. Dis. 2, 157–168 (2016).

    CAS  PubMed  Google Scholar 

  94. Gaddy, J. A. et al. Role of acinetobactin-mediated iron acquisition functions in the interaction of Acinetobacter baumannii strain ATCC 19606T with human lung epithelial cells, Galleria mellonella caterpillars, and mice. Infect. Immun. 80, 1015–1024 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Proschak, A. et al. Structure and biosynthesis of fimsbactins A-F, siderophores from Acinetobacter baumannii and Acinetobacter baylyi. Chembiochem 14, 633–638 (2013).

    CAS  PubMed  Google Scholar 

  96. Penwell, W. F. et al. Discovery and characterization of new hydroxamate siderophores, baumannoferrin A and B, produced by Acinetobacter baumannii. Chembiochem 16, 1896–1904 (2015).

    CAS  PubMed  Google Scholar 

  97. Zackular, J. P., Chazin, W. J. & Skaar, E. P. Nutritional immunity: S100 proteins at the host-pathogen interface. J. Biol. Chem. 290, 18991–18998 (2015).

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Moore, J. L. et al. Imaging mass spectrometry for assessing temporal proteomics: analysis of calprotectin in Acinetobacter baumannii pulmonary infection. Proteomics 14, 820–828 (2014).

    CAS  PubMed  Google Scholar 

  99. Hood, M. I. et al. Identification of an Acinetobacter baumannii zinc acquisition system that facilitates resistance to calprotectin-mediated zinc sequestration. PLoS Pathog. 8, e1003068 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Mortensen, B. L., Rathi, S., Chazin, W. J. & Skaar, E. P. Acinetobacter baumannii response to host-mediated zinc limitation requires the transcriptional regulator Zur. J. Bacteriol. 196, 2616–2626 (2014).

    PubMed Central  PubMed  Google Scholar 

  101. Nairn, B. L. et al. The response of Acinetobacter baumannii to zinc starvation. Cell Host Microbe 19, 826–836 (2016). This paper details the importance of micronutrient acquisition systems, specifically of zinc, for A. baumannii virulence.

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Juttukonda, L. J., Chazin, W. J. & Skaar, E. P. Acinetobacter baumannii coordinates urea metabolism with metal import to resist host-mediated metal limitation. mBio 7, e01475-16 (2016).

    PubMed Central  PubMed  Google Scholar 

  103. Johnson, T. L., Waack, U., Smith, S., Mobley, H. & Sandkvist, M. Acinetobacter baumannii is dependent on the type II secretion system and its substrate LipA for lipid utilization and in vivo fitness. J. Bacteriol. 198, 711–719 (2015).

    PubMed  Google Scholar 

  104. Harding, C. M., Kinsella, R. L., Palmer, L. D., Skaar, E. P. & Feldman, M. F. Medically relevant acinetobacter species require a type II secretion system and specific membrane-associated chaperones for the export of multiple substrates and full virulence. PLoS Pathog. 12, e1005391 (2016).

    PubMed Central  PubMed  Google Scholar 

  105. Liu, C. C., Kuo, H. Y., Tang, C. Y., Chang, K. C. & Liou, M. L. Prevalence and mapping of a plasmid encoding a type IV secretion system in Acinetobacter baumannii. Genomics 104, 215–223 (2014).

    CAS  PubMed  Google Scholar 

  106. Weber, B. S. et al. Genomic and functional analysis of the type VI secretion system in Acinetobacter. PLoS ONE 8, e55142 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Carruthers, M. D., Nicholson, P. A., Tracy, E. N. & Munson, R. S. Jr. Acinetobacter baumannii utilizes a type VI secretion system for bacterial competition. PLoS ONE 8, e59388 (2013).

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Weber, B. S., Kinsella, R. L., Harding, C. M. & Feldman, M. F. The secrets of Acinetobacter secretion. Trends Microbiol. 25, 532–545 (2017).

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Bentancor, L. V. et al. Evaluation of the trimeric autotransporter Ata as a vaccine candidate against Acinetobacter baumannii infections. Infect. Immun. 80, 3381–3388 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Weber, B. S., Ly, P. M., Irwin, J. N., Pukatzki, S. & Feldman, M. F. A multidrug resistance plasmid contains the molecular switch for type VI secretion in Acinetobacter baumannii. Proc. Natl Acad. Sci. USA 112, 9442–9447 (2015). This paper describes a novel form of plasmid- mediated regulation of the A. baumannii T6SS.

    CAS  PubMed  Google Scholar 

  111. Kinsella, R. L. et al. Defining the interaction of the protease CpaA with its type II secretion-chaperone CpaB and its contribution to virulence in Acinetobacter species. J. Biol. Chem. http://dx.doi.org/10.1074/jbc.M117.808394 (2017).

  112. Tilley, D., Law, R., Warren, S., Samis, J. A. & Kumar, A. CpaA a novel protease from Acinetobacter baumannii clinical isolates deregulates blood coagulation. FEMS Microbiol. Lett. 356, 53–61 (2014).

    CAS  PubMed  Google Scholar 

  113. Chan, A. P. et al. A novel method of consensus pan-chromosome assembly and large-scale comparative analysis reveal the highly flexible pan-genome of Acinetobacter baumannii. Genome Biol. 16, 143 (2015).

    PubMed Central  PubMed  Google Scholar 

  114. Bhuiyan, M. S. et al. Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis. Proc. Natl Acad. Sci. USA 113, 9599–9604 (2016). This paper highlights the role of the innate immune response, particularly neutrophils, in A. baumannii clearance and defines phenylacetic acid as a potent chemoattractant for phagocytes.

    CAS  PubMed  Google Scholar 

  115. Cabral, M. P. et al. Design of live attenuated bacterial vaccines based on D-glutamate auxotrophy. Nat. Commun. 8, 15480 (2017). This paper describes a promising live attenuated vaccine candidate for A. baumannii.

    CAS  PubMed  Google Scholar 

  116. Jacobs, A. C. et al. AB5075, a highly virulent isolate of Acinetobacter baumannii, as a model strain for the evaluation of pathogenesis and antimicrobial treatments. mBio 5, e01076-14 (2014).

    PubMed Central  PubMed  Google Scholar 

  117. Lee, J. C. et al. Adherence of Acinetobacter baumannii strains to human bronchial epithelial cells. Res. Microbiol. 157, 360–366 (2006).

    CAS  PubMed  Google Scholar 

  118. Weidensdorfer, M. et al. Analysis of endothelial adherence of Bartonella henselae and Acinetobacter baumannii using a dynamic human ex vivo infection model. Infect. Immun. 84, 711–722 (2015).

    PubMed  Google Scholar 

  119. Brossard, K. A. & Campagnari, A. A. The Acinetobacter baumannii biofilm-associated protein plays a role in adherence to human epithelial cells. Infect. Immun. 80, 228–233 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  120. Choi, C. H., Lee, J. S., Lee, Y. C., Park, T. I. & Lee, J. C. Acinetobacter baumannii invades epithelial cells and outer membrane protein A mediates interactions with epithelial cells. BMC Microbiol. 8, 216 (2008).

    PubMed Central  PubMed  Google Scholar 

  121. Noto, M. J. et al. Toll-like receptor 9 contributes to defense against Acinetobacter baumannii infection. Infect. Immun. 83, 4134–4141 (2015).

    CAS  PubMed Central  PubMed  Google Scholar 

  122. Bist, P. et al. The Nod1, Nod2, and Rip2 axis contributes to host immune defense against intracellular Acinetobacter baumannii infection. Infect. Immun. 82, 1112–1122 (2014).

    PubMed Central  PubMed  Google Scholar 

  123. March, C. et al. Dissection of host cell signal transduction during Acinetobacter baumannii-triggered inflammatory response. PLoS ONE 5, e10033 (2010).

    PubMed Central  PubMed  Google Scholar 

  124. Feng, Z. et al. Epithelial innate immune response to Acinetobacter baumannii challenge. Infect. Immun. 82, 4458–4465 (2014).

    PubMed Central  PubMed  Google Scholar 

  125. Breslow, J. M. et al. Innate immune responses to systemic Acinetobacter baumannii infection in mice: neutrophils, but not interleukin-17, mediate host resistance. Infect. Immun. 79, 3317–3327 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  126. van Faassen, H. et al. Neutrophils play an important role in host resistance to respiratory infection with Acinetobacter baumannii in mice. Infect. Immun. 75, 5597–5608 (2007).

    CAS  PubMed Central  PubMed  Google Scholar 

  127. Qiu, H., Kuolee, R., Harris, G. & Chen, W. Role of NADPH phagocyte oxidase in host defense against acute respiratory Acinetobacter baumannii infection in mice. Infect. Immun. 77, 1015–1021 (2009).

    CAS  PubMed  Google Scholar 

  128. Weber, B. S. et al. Genetic dissection of the type VI secretion system in acinetobacter and identification of a novel peptidoglycan hydrolase, TagX, required for its biogenesis. mBio 7, e01253-16 (2016).

    PubMed Central  PubMed  Google Scholar 

  129. Arroyo, L. A. et al. The pmrCAB operon mediates polymyxin resistance in Acinetobacter baumannii ATCC 17978 and clinical isolates through phosphoethanolamine modification of lipid A. Antimicrob. Agents Chemother. 55, 3743–3751 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  130. Chin, C. Y., Gregg, K. A., Napier, B. A., Ernst, R. K. & Weiss, D. S. A. PmrB-regulated deacetylase required for lipid A modification and polymyxin resistance in Acinetobacter baumannii. Antimicrob. Agents Chemother. 59, 7911–7914 (2015).

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

During the preparation of this Review article, C.M.H. was funded as a W.M. Keck Postdoctoral Fellow. The efforts of S.W.H. and M.F.F. were funded by a US National Institutes of Health (NIH) grant (1R01AI125363-01).

Author information

Authors and Affiliations

Authors

Contributions

C.M.H., S.W.H. and M.F.F. researched data for the article, made substantial contributions to discussions of the content and wrote the article. C.M.H. and M.F.F. also reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Mario F. Feldman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

PowerPoint slides

Glossary

Lipooligosaccharide

(LOS). A macromolecule consisting of lipid A and a core oligosaccharide found in the outer leaflet of the outer membrane of Gram-negative bacteria. Lipid A is also considered an endotoxin and is the ligand for Toll-like receptor 4.

Catalase

An enzyme that detoxifies hydrogen peroxide into water and oxygen.

Phagocytosis

The process used by many immune cells, including macrophages, to engulf invading bacteria.

Two-component regulatory system

A two-part relay system used by bacteria for sensing and responding to environmental stimuli, consisting of a membrane-bound histidine kinase and a soluble response regulator.

Surface-associated motility

A mechanism of bacterial translocation observed on semisolid surfaces and unique to Acinetobacter spp., which is not dependent on pili.

Twitching motility

A mechanism of bacterial translocation dependent on repetitive rounds of type IV pili extension and retraction broadly used by many bacteria.

Opaque phase variants

A subset of an Acinetobacter baumannii population that has an opaque appearance when viewed under a microscope and differs from the translucent form in terms of both appearance and virulence.

Glycoconjugates

Macromolecules composed of a carbohydrate covalently attached to at least one other lipid or protein molecule.

Lipopolysaccharide

(LPS). A macromolecule consisting of lipid A, a core oligosaccharide and a polysaccharide O antigen found in the outer leaflet of the outer membrane of Gram-negative bacteria.

Complement-mediated killing

A process that is part of the innate immune system consisting of soluble proteins in the blood that coordinately bind to an invading pathogen, triggering either lysis or the recruitment of immune cells to clear the pathogen.

O-glycosylation

The covalent attachment of a carbohydrate moiety to the hydroxyl group of a serine or threonine in a polypeptide.

Siderophores

High-affinity iron-binding molecules secreted by many bacterial pathogens to scavenge iron.

Adhesion

The process whereby bacteria associate with a surface, either a biotic surface (for example, human cells) or an abiotic surface (for example, medical equipment and devices).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harding, C., Hennon, S. & Feldman, M. Uncovering the mechanisms of Acinetobacter baumannii virulence. Nat Rev Microbiol 16, 91–102 (2018). https://doi.org/10.1038/nrmicro.2017.148

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro.2017.148

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing