1887

Abstract

() is an emerging opportunistic pathogen associated to nosocomial infections. The rapid increase in multidrug resistance (MDR) among strains underscores the urgency of understanding how this pathogen evolves in the clinical environment. We conducted here a whole-genome sequence comparative analysis of three phylogenetically and epidemiologically related MDR strains from Argentinean hospitals, assigned to the CC104/CC15 clonal complex. While the Ab244 strain was carbapenem-susceptible, Ab242 and Ab825, isolated after the introduction of carbapenem therapy, displayed resistance to these last resource β-lactams. We found a high chromosomal synteny among the three strains, but significant differences at their accessory genomes. Most importantly, carbapenem resistance in Ab242 and Ab825 was attributed to the acquisition of a Rep_3 family plasmid carrying a gene. Other differences involved a genomic island carrying resistance to toxic compounds and a Tn element exclusive to Ab244 and Ab825, respectively. Also remarkably, 44 insertion sequences (ISs) were uncovered in Ab825, in contrast with the 14 and 11 detected in Ab242 and Ab244, respectively. Moreover, Ab825 showed a higher killing capacity as compared to the other two strains in the infection model. A search for virulence and persistence determinants indicated the loss or IS-mediated interruption of genes encoding many surface-exposed macromolecules in Ab825, suggesting that these events are responsible for its higher relative virulence. The comparative genomic analyses of the CC104/CC15 strains conducted here revealed the contribution of acquired mobile genetic elements such as ISs and plasmids to the adaptation of to the clinical setting.

Funding
This study was supported by the:
  • Guillermo Daniel Repizo , Conicet , (Award PIP2017-11220170100377CO)
  • Jorgelina Moran-Barrio , ANPCyT , (Award PICT-2017-3536)
  • Alejandro M Viale , Agencia Nacional de Promoción Científica y Técnológica , (Award PICT-2015-1072)
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2020-03-26
2020-06-03
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References

  1. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008; 21:538582 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  2. Antunes LCS, Visca P, Towner KJ. Acinetobacter baumannii: evolution of a global pathogen. Pathog Dis 2014; 71:292–301 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  3. Wong D, Nielsen TB, Bonomo RA, Pantapalangkoor P, Luna B et al. Clinical and pathophysiological overview of Acinetobacter infections: a century of challenges. Clin Microbiol Rev 2017; 30:409–447 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  4. Diancourt L, Passet V, Nemec A, Dijkshoorn L, Brisse S. The population structure of Acinetobacter baumannii: expanding multiresistant clones from an ancestral susceptible genetic pool. PLoS One 2010; 5:e10034 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  5. Roca I, Espinal P, Vila-Farrés X, Vila J. The Acinetobacter baumannii oxymoron: commensal hospital dweller turned pan-drug-resistant menace. Front Microbiol 2012; 3:148 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  6. Mussi M, Limansky A, Viale A. Acquisition of resistance to carbapenems in multidrug-resistant clinical strains of. Antimicrobial Agents and Chemother 2005; 49:1432–1440 [CrossRef]
    [Google Scholar]
  7. Mussi MA, Relling VM, Limansky AS, Viale AM. CarO, an Acinetobacter baumannii outer membrane protein involved in carbapenem resistance, is essential for L-ornithine uptake. FEBS Lett 2007; 581:5573–5578 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  8. Mussi MA, Limansky AS, Relling V, Ravasi P, Arakaki A et al. Horizontal gene transfer and assortative recombination within the Acinetobacter baumannii clinical population provide genetic diversity at the single carO gene, encoding a major outer membrane protein channel. J Bacteriol 2011; 193:4736–4748 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  9. Ravasi P, Limansky AS, Rodriguez RE, Viale AM, Mussi MA. ISAba825, a functional insertion sequence modulating genomic plasticity and bla(OXA-58) expression in Acinetobacter baumannii. Antimicrob Agents Chemother 2011; 55:917–920 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  10. Morán-Barrio J, Cameranesi MM, Relling V, Limansky AS, Brambilla L et al. The Acinetobacter outer membrane contains multiple specific channels for carbapenem β-lactams as revealed by kinetic characterization analyses of imipenem permeation into Acinetobacter baylyi cells. Antimicrob Agents Chemother 2017; 61: [CrossRef][PubMed][PubMed]
    [Google Scholar]
  11. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M et al. Discovery, research, and development of new antibiotics: the who priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018; 18:318327 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  12. Touchon M, Cury J, Yoon E-J, Krizova L, Cerqueira GC et al. The genomic diversification of the whole Acinetobacter genus: origins, mechanisms, and consequences. Genome Biol Evol 2014; 6:2866–2882 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  13. Harding CM, Hennon SW, Feldman MF. Uncovering the mechanisms of Acinetobacter baumannii virulence. Nat Rev Microbiol 2018; 16:91–102 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  14. Lee C-R, Lee JH, Park M, Park KS, Bae IK et al. Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options. Front Cell Infect Microbiol 2017; 7:55 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  15. Nigro SJ, Post V, Hall RM. The multiresistant Acinetobacter baumannii European clone I type strain RUH875 (A297) carries a genomic antibiotic resistance island AbaR21, plasmid pRAY and a cluster containing ISAba1-sul2-CR2-strB-strA. J Antimicrob Chemother 2011; 66:1928–1930 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  16. Chan AP, Sutton G, DePew J, Krishnakumar R, Choi Y 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 2015; 16:143 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  17. Nigro SJ, Hall RM. Structure and context of Acinetobacter transposons carrying the oxa23 carbapenemase gene. J Antimicrob Chemother 2016; 71:1135–1147 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  18. Blackwell GA, Hall RM. The tet39 Determinant and the msrE-mphE Genes in Acinetobacter Plasmids Are Each Part of Discrete Modules Flanked by Inversely Oriented pdif (XerC-XerD) Sites. Antimicrob Agents Chemother 2017; 61: [CrossRef][PubMed][PubMed]
    [Google Scholar]
  19. Adams MD, Bishop B, Wright MS. Quantitative assessment of insertion sequence impact on bacterial genome architecture. Microb Genom 2016; 2:e000062 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  20. Wright MS, Mountain S, Beeri K, Adams MD. Assessment of insertion sequence mobilization as an adaptive response to oxidative stress in Acinetobacter baumannii using IS-seq. J Bacteriol 2017; 199: [CrossRef][PubMed][PubMed]
    [Google Scholar]
  21. Karah N, Sundsfjord A, Towner K, Samuelsen Ørjan. Insights into the global molecular epidemiology of carbapenem non-susceptible clones of Acinetobacter baumannii. Drug Resist Updat 2012; 15:237–247 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  22. Geisinger E, Huo W, Hernandez-Bird J, Isberg RR. Acinetobacter baumannii: Envelope Determinants That Control Drug Resistance, Virulence, and Surface VariEnvelope Determinants That Control Drug Resistance, Virulence, and Surface Variability. Annu Rev Microbiol 2019; 73:481–506
    [Google Scholar]
  23. Repizo GD, Viale AM, Borges V, Cameranesi MM, Taib N et al. The environmental Acinetobacter baumannii isolate DSM30011 reveals clues into the preantibiotic era genome diversity, virulence potential, and niche range of a predominant nosocomial pathogen. Genome Biol Evol 2017; 9:22922307 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  24. Yakkala H, Samantarrai D, Gribskov M, Siddavattam D. Comparative genome analysis reveals niche-specific genome expansion in Acinetobacter baumannii strains. PLoS One 2019; 14:e0218204 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  25. Snitkin ES, Zelazny AM, Montero CI, Stock F, Mijares L et al. Genome-Wide recombination drives diversification of epidemic strains of Acinetobacter baumannii. Proc Natl Acad Sci U S A 2011; 108:13758–13763 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  26. Wright MS, Haft DH, Harkins DM, Perez F, Hujer KM et al. New insights into dissemination and variation of the health care-associated pathogen Acinetobacter baumannii from genomic analysis. mBio 2014; 5:e00963-13 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  27. Limansky AS, Zamboni MI, Guardati MC, Rossignol G, Campos E et al. Evaluation of phenotypic and genotypic markers for clinical strains of Acinetobacter baumannii. Medicina 2004; 64:306–312[PubMed][PubMed]
    [Google Scholar]
  28. Mussi MA, Limansky AS, Viale AM. Acquisition of resistance to carbapenems in multidrug-resistant clinical strains of Acinetobacter baumannii: natural insertional inactivation of a gene encoding a member of a novel family of beta-barrel outer membrane proteins. Antimicrob Agents Chemother 2005; 49:1432–1440 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  29. Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing, Document M100S, 26th ed. Wayne, PA: 2016
    [Google Scholar]
  30. Darling AE, Mau B, Perna NT. ProgressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PLoS One 2010; 5:e11147 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  31. Gao F, Zhang C-T. Ori-Finder: a web-based system for finding oriCs in unannotated bacterial genomes. BMC Bioinformatics 2008; 9:79 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  32. Siguier P, Perochon J, Lestrade L, Mahillon J, Chandler M. ISfinder: the reference centre for bacterial insertion sequences. Nucleic Acids Res 2006; 34:D32D36 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  33. Arndt D, Grant JR, Marcu A, Sajed T, Pon A et al. PHASTER: a better, faster version of the PHAST phage search tool. Nucleic Acids Res 2016; 44:W16W21 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  34. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 2012; 67:2640–2644 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  35. Jolley KA, Maiden MCJ. BIGSdb: scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics 2010; 11:595 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  36. Antunes LCS, Imperi F, Towner KJ, 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 2011; 162:279284 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  37. Repizo GD, Gagné S, Foucault-Grunenwald M-L, Borges V, Charpentier X et al. Differential role of the T6SS in Acinetobacter baumannii virulence. PLoS One 2015; 10:e0138265 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  38. Clímaco EC, Oliveira MLde, Pitondo-Silva A, Oliveira MG, Medeiros M et al. Clonal complexes 104, 109 and 113 playing a major role in the dissemination of OXA-carbapenemase-producing Acinetobacter baumannii in Southeast Brazil. Infect Genet Evol 2013; 19:127–133 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  39. Stietz MS, Ramírez MS, Vilacoba E, Merkier AK, Limansky AS et al. Acinetobacter baumannii extensively drug resistant lineages in Buenos Aires hospitals differ from the International clones I-III. Infect Genet Evol 2013; 14:294–301 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  40. Smith MG, Gianoulis TA, Pukatzki S, Mekalanos JJ, Ornston LN et al. New insights into Acinetobacter baumannii pathogenesis revealed by high-density pyrosequencing and transposon mutagenesis. Genes Dev 2007; 21:601–614 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  41. Repizo GD, Espariz M, Seravalle JL, Salcedo SP. Bioinformatic analysis of the type VI secretion system and its potential toxins in the Acinetobacter genus. Front Microbiol 2019; 10: [CrossRef]
    [Google Scholar]
  42. De Gregorio E, Zarrilli R, Di Nocera PP. Contact-dependent growth inhibition systems in Acinetobacter. Sci Rep 2019; 9:154 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  43. Roussin M, Rabarioelina S, Cluzeau L, Cayron J, Lesterlin C et al. Identification of a Contact-Dependent Growth Inhibition (CDI) System That Reduces Biofilm Formation and Host Cell Adhesion of Acinetobacter baumannii DSM30011 Strain. Front Microbiol 2019; 10:2450 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  44. Wright MS, Haft DH, Harkins DM, Perez F, Hujer KM et al. New insights into dissemination and variation of the health care-associated pathogen Acinetobacter baumannii from genomic analysis. mBio 2014; 5:e00963-13 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  45. Kim DH, Jung S-I, Kwon KT, Ko KS. Occurrence of diverse AbGRI1-type genomic islands in Acinetobacter baumannii global clone 2 isolates from South Korea. Antimicrob Agents Chemother 2017; 61: [CrossRef][PubMed][PubMed]
    [Google Scholar]
  46. Seputiene V, Povilonis J, Sužiedeliene E. Novel variants of AbaR resistance islands with a common backbone in Acinetobacter baumannii isolates of European clone II. Antimicrob Agents Chemother 2012; 56:1969–1973 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  47. Post V, White PA, Hall RM. Evolution of AbaR-type genomic resistance islands in multiply antibiotic-resistant Acinetobacter baumannii. J Antimicrob Chemother 2010; 65:1162–1170 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  48. Liu F, Zhu Y, Yi Y, Lu N, Zhu B et al. Comparative genomic analysis of Acinetobacter baumannii clinical isolates reveals extensive genomic variation and diverse antibiotic resistance determinants. BMC Genomics 2014; 15:1163 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  49. Al-Jabri Z, Zamudio R, Horvath-Papp E, Ralph JD, Al-Muharrami Z et al. Integrase-Controlled Excision of Metal-Resistance Genomic Islands in Acinetobacter baumannii. Genes 2018; 9:366 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  50. Farrugia DN, Elbourne LDH, Mabbutt BC, Paulsen IT. A novel family of integrases associated with prophages and genomic islands integrated within the tRNA-dihydrouridine synthase A (dusA) gene. Nucleic Acids Res 2015; 43:4547–4557 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  51. Ghisotti D, Finkel S, Halling C, Dehò G, Sironi G et al. Nonessential region of bacteriophage P4: DNA sequence, transcription, gene products, and functions. J Virol 1990; 64:24–36 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  52. Costa AR, Monteiro R, Azeredo J. Genomic analysis of Acinetobacter baumannii prophages reveals remarkable diversity and suggests profound impact on bacterial virulence and fitness. Sci Rep 2018; 8:15346 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  53. Babu MM, Iyer LM, Balaji S, Aravind L. The natural history of the WRKY-GCM1 zinc fingers and the relationship between transcription factors and transposons. Nucleic Acids Res 2006; 34:65056520 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  54. Eaves-Pyles T, Allen CA, Taormina J, Swidsinski A, Tutt CB et al. Escherichia coli isolated from a Crohn's disease patient adheres, invades, and induces inflammatory responses in polarized intestinal epithelial cells. Int J Med Microbiol 2008; 298:397–409 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  55. Chai B, Wang H, Chen X. Draft genome sequence of high-melanin-yielding Aeromonas media strain Ws. J Bacteriol 2012; 194:66936694 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  56. Carattoli A. Plasmids and the spread of resistance. Int J Med Microbiol 2013; 303:298–304 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  57. Cameranesi MM, Morán-Barrio J, Limansky AS, Repizo GD, Viale AM. Site-Specific Recombination at XerC/D Sites Mediates the Formation and Resolution of Plasmid Co-integrates Carrying a blaOXA-58- and TnaphA6-Resistance Module in Acinetobacter baumannii. Front Microbiol 2018; 9:66 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  58. Mindlin S, Beletsky A, Mardanov A, Petrova M. Adaptive dif modules in permafrost strains of Acinetobacter lwoffii and their distribution and abundance among present day Acinetobacter strains. Front Microbiol 2019; 10:1–11 [CrossRef]
    [Google Scholar]
  59. Brovedan M, Repizo GD, Marchiaro P, Viale AM, Limansky A. Characterization of the diverse plasmid pool harbored by the blaNDM-1-containing Acinetobacter bereziniae HPC229 clinical strain. PLoS One 2019; 14:e0220584 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  60. Evans BA, Amyes SGB. Oxa β-lactamases. Clin Microbiol Rev 2014; 27:241–263 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  61. Lopes BS, Amyes SGB. Role of ISAba1 and ISAba125 in governing the expression of blaADC in clinically relevant Acinetobacter baumannii strains resistant to cephalosporins. J Med Microbiol 2012; 61:11031108 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  62. Segal H, Jacobson RK, Garny S, Bamford CM, Elisha BG. Extended -10 promoter in ISAba-1 upstream of blaOXA-23 from Acinetobacter baumannii. Antimicrob Agents Chemother 2007; 51:3040–3041 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  63. Tian G-B, Adams-Haduch JM, Taracila M, Bonomo RA, Wang H-N et al. Extended-Spectrum AmpC cephalosporinase in Acinetobacter baumannii: ADC-56 confers resistance to cefepime. Antimicrob Agents Chemother 2011; 55:4922–4925 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  64. Perreten V, Boerlin P. A new sulfonamide resistance gene (sul3) in Escherichia coli is widespread in the pig population of Switzerland. Antimicrob Agents Chemother 2003; 47:1169–1172 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  65. Byrne-Bailey KG, Gaze WH, Kay P, Boxall ABA, Hawkey PM et al. Prevalence of sulfonamide resistance genes in bacterial isolates from manured agricultural soils and pig slurry in the United Kingdom. Antimicrob Agents Chemother 2009; 53:696–702 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  66. Post V, White PA, Hall RM. Evolution of AbaR-type genomic resistance islands in multiply antibiotic-resistant Acinetobacter baumannii. J Antimicrob Chemother 2010; 65:1162–1170 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  67. Hamidian M, Hall RM. The resistance gene complement of D4, a multiply antibiotic-resistant ST25 Acinetobacter baumannii isolate, resides in two genomic islands and a plasmid. J Antimicrob Chemother 2016; 71:1730–1732 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  68. Falagas ME, Vardakas KZ, Roussos NS. Trimethoprim/Sulfamethoxazole for Acinetobacter spp.: a review of current microbiological and clinical evidence. Int J Antimicrob Agents 2015; 46:231–241 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  69. Lawley TD, Burland V, Taylor DE. Analysis of the complete nucleotide sequence of the tetracycline-resistance transposon Tn10. Plasmid 2000; 43:235–239 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  70. Peleg AY, Jara S, Monga D, Eliopoulos GM, Moellering RC et al. Galleria mellonella as a model system to study Acinetobacter baumannii pathogenesis and therapeutics. Antimicrob Agents Chemother 2009; 53:2605–2609 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  71. Lee C-R, Lee JH, Park M, Park KS, Bae IK et al. Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options. Front Cell Infect Microbiol 2017; 7:55 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  72. Iwashkiw JA, Seper A, Weber BS, Scott NE, Vinogradov E et al. Identification of a general O-linked protein glycosylation system in Acinetobacter baumannii and its role in virulence and biofilm formation. PLoS Pathog 2012; 8:e1002758 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  73. Kenyon JJ, Hall RM. Variation in the complex carbohydrate biosynthesis loci of Acinetobacter baumannii genomes. PLoS One 2013; 8:e62160 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  74. Singh JK, Adams FG, Brown MH. Diversity and function of capsular polysaccharide in Acinetobacter baumannii. Front Microbiol 2019; 10:1–8 [CrossRef]
    [Google Scholar]
  75. Hu D, Liu B, Dijkshoorn L, Wang L, Reeves PR. Diversity in the major polysaccharide antigen of Acinetobacter baumannii assessed by DNA sequencing, and development of a molecular serotyping scheme. PLoS One 2013; 8:e70329–13 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  76. Liu MA, Morris P, Reeves PR. Wzx flippases exhibiting complex O-unit preferences require a new model for Wzx-substrate interactions. Microbiologyopen 2019; 8:e00655 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  77. Kenyon JJ, Nigro SJ, Hall RM. Variation in the OC locus of Acinetobacter baumannii genomes predicts extensive structural diversity in the lipooligosaccharide. PLoS One 2014; 9:e107833 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  78. Gaddy JA, Arivett BA, McConnell MJ, López-Rojas R, Pachón J 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 2012; 80:1015–1024 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  79. Mortensen BL, Skaar EP. The contribution of nutrient metal acquisition and metabolism to Acinetobacter baumannii survival within the host. Front Cell Infect Microbiol 2013; 3:95 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  80. Runci F, Gentile V, Frangipani E, Rampioni G, Leoni L et al. Contribution of active iron uptake to Acinetobacter baumannii pathogenicity. Infect Immun 2019; 87: [CrossRef][PubMed][PubMed]
    [Google Scholar]
  81. Gaddy JA, Arivett BA, McConnell MJ, López-Rojas R, Pachón J, Actis LA, Rafael LR 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 2012; 80:1015–1024 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  82. Ou H-Y, Kuang SN, He X, Molgora BM, Ewing PJ et al. Complete genome sequence of hypervirulent and outbreak-associated Acinetobacter baumannii strain LAC-4: epidemiology, resistance genetic determinants and potential virulence factors. Sci Rep 2015; 5:8643 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  83. Penwell WF, DeGrace N, Tentarelli S, Gauthier L, Gilbert CM et al. Discovery and characterization of new hydroxamate siderophores, Baumannoferrin A and B, produced by Acinetobacter baumannii. Chembiochem 2015; 16:1896–1904 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  84. Waack U, Warnock M, Yee A, Huttinger Z, Smith S et al. CpaA is a glycan-specific Adamalysin-like protease secreted by Acinetobacter baumannii that inactivates coagulation factor XII. mBio 2018; 9:e01606-18 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  85. Weber BS, Harding CM, Feldman MF. Pathogenic Acinetobacter: from the cell surface to infinity and beyond. J Bacteriol 2016; 198:880–887 [CrossRef]
    [Google Scholar]
  86. Harding CM, Pulido MR, Di Venanzio G, Kinsella RL, Webb AI et al. Pathogenic Acinetobacter species have a functional type I secretion system and contact-dependent inhibition systems. J Biol Chem 2017; 292:9075–9087 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  87. Pierson LS, Pierson EA. Metabolism and function of phenazines in bacteria: impacts on the behavior of bacteria in the environment and biotechnological processes. Appl Microbiol Biotechnol 2010; 86:16591670 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  88. Karuppiah V, Thistlethwaite A, Dajani R, Warwicker J, Derrick JP. Structure and mechanism of the bifunctional CinA enzyme from Thermus thermophilus. J Biol Chem 2014; 289:33187–33197 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  89. Eijkelkamp BA, Stroeher UH, Hassan KA, Paulsen IT, Brown MH. Comparative analysis of surface-exposed virulence factors of Acinetobacter baumannii. BMC Genomics 2014; 15:1020 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  90. Zeidler S, Müller V. Coping with low water activities and osmotic stress in Acinetobacter baumannii: significance, current status and perspectives. Environ Microbiol 2019; 21:2212–2230 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  91. Stahl J, Bergmann H, Göttig S, Ebersberger I, Averhoff B. Acinetobacter baumannii virulence is mediated by the concerted action of three phospholipases D. PLoS One 2015; 10:e0138360–19 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  92. Weber BS, Hennon SW, Wright MS, Scott NE, de Berardinis V 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 2016; 7:e01253-16 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  93. Li L, Wang Y-N, Jia H-B, Wang P, Dong J-F et al. The type VI secretion system protein AsaA in Acinetobacter baumannii is a periplasmic protein physically interacting with TssM and required for T6SS assembly. Sci Rep 2019; 9:9438 [CrossRef]
    [Google Scholar]
  94. Jones CL, Clancy M, Honnold C, Singh S, Snesrud E et al. Fatal outbreak of an emerging clone of extensively drug-resistant Acinetobacter baumannii with enhanced virulence. Clin Infect Dis 2015; 61:145–154 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  95. Repizo GD. Prevalence of Acinetobacter baumannii strains expressing the type 6 secretion system in patients with bacteremia. Virulence 2017; 8:10991101 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  96. Gebhardt MJ, Gallagher LA, Jacobson RK, Usacheva EA, Peterson LR et al. Joint transcriptional control of virulence and resistance to antibiotic and environmental stress in Acinetobacter baumannii. mBio 2015; 6:e01660-15 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  97. Di Venanzio G, Moon KH, Weber BS, Lopez J, Ly PM et al. Multidrug-resistant plasmids repress chromosomally encoded T6SS to enable their dissemination. Proc Natl Acad Sci U S A 2019; 116:1378–1383 [CrossRef]
    [Google Scholar]
  98. Zhang L, Liang W, Shu-Gen Xu JM, Di Y-Y LH-H, Wang Y et al. CarO promotes adhesion and colonization of Acinetobacter baumannii through inhibiting NF-кB pathways. Int J Clin Exp Med 2019; 12:2518–2524
    [Google Scholar]
  99. Clímaco EC, Oliveira MLde, Pitondo-Silva A, Oliveira MG, Medeiros M et al. Clonal complexes 104, 109 and 113 playing a major role in the dissemination of OXA-carbapenemase-producing Acinetobacter baumannii in Southeast Brazil. Infect Genet Evol 2013; 19:127–133 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  100. Ramírez MS, Vilacoba E, Stietz MS, Merkier AK, Jeric P et al. Spreading of AbaR-type genomic islands in multidrug resistance Acinetobacter baumannii strains belonging to different clonal complexes. Curr Microbiol 2013; 67:9–14 [CrossRef][PubMed][PubMed]
    [Google Scholar]
  101. Palmer KL, Gilmore MS. Multidrug-Resistant enterococci lack CRISPR-Cas. mBio 2010; 1:e00227-10 [CrossRef][PubMed][PubMed]
    [Google Scholar]
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