1887

Abstract

Acinetobacter baumannii causes severe, fulminant, community-acquired pneumonia (CAP) in tropical and subtropical regions. We compared the population structure, virulence and antimicrobial resistance determinants of northern Australian community-onset A. baumannii strains with local and global strains. We performed whole-genome sequencing on 55 clinical and five throat colonization A. baumannii isolates collected in northern Australia between 1994 and 2016. Clinical isolates included CAP (n=41), healthcare-associated pneumonia (n=7) and nosocomial bloodstream (n=7) isolates. We also included 93 publicly available international A. baumannii genome sequences in the analyses. Patients with A. baumannii CAP were almost all critically unwell; 82 % required intensive care unit admission and 18 % died during their inpatient stay. Whole-genome phylogenetic analysis demonstrated that community-onset strains were not phylogenetically distinct from nosocomial strains. Some non-multidrug-resistant local strains were closely related to multidrug-resistant strains from geographically distant locations. Pasteur sequence type (ST)10 was the dominant ST and accounted for 31/60 (52 %) northern Australian strains; the remainder belonged to a diverse range of STs. The most recent common ancestor for ST10 was estimated to have occurred in 1738 (95 % highest posterior density, 1626–1826), with evidence of multiple introduction events between Australia and Southeast Asia between then and the present day. Virulence genes associated with biofilm formation and the type 6 secretion system (T6SS) were absent in many strains, and were not associated with in-hospital mortality. All strains were susceptible to gentamicin and meropenem; none carried an AbaR resistance island. Our results suggest that international dissemination of A. baumannii is occurring in the community on a contemporary timescale. Genes associated with biofilm formation and the T6SS may not be required for survival in community niches. The relative contributions of host and bacterial factors to the clinical severity of community-onset A. baumannii infection require further investigation.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000258
2019-02-26
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/mgen/5/3/mgen000258.html?itemId=/content/journal/mgen/10.1099/mgen.0.000258&mimeType=html&fmt=ahah

References

  1. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008; 21:538–582 [View Article][PubMed]
    [Google Scholar]
  2. 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 [View Article][PubMed]
    [Google Scholar]
  3. Davis JS, McMillan M, Swaminathan A, Kelly JA, Piera KE et al. A 16-year prospective study of community-onset bacteremic Acinetobacter pneumonia: low mortality with appropriate initial empirical antibiotic protocols. Chest 2014; 146:1038–1045 [View Article][PubMed]
    [Google Scholar]
  4. Anstey NM, Currie BJ, Withnall KM. Community-acquired Acinetobacter pneumonia in the Northern Territory of Australia. Clin Infect Dis 1992; 14:83–91 [View Article][PubMed]
    [Google Scholar]
  5. Dexter C, Murray GL, Paulsen IT, Peleg AY. Community-acquired Acinetobacter baumannii : clinical characteristics, epidemiology and pathogenesis. Expert Rev Anti Infect Ther 2015; 13:567–573 [View Article]
    [Google Scholar]
  6. Harding CM, Hennon SW, Feldman MF. Uncovering the mechanisms of Acinetobacter baumannii virulence. Nat Rev Microbiol 2018; 16:91–102 [View Article][PubMed]
    [Google Scholar]
  7. Camarena L, Bruno V, Euskirchen G, Poggio S, Snyder M. Molecular mechanisms of ethanol-induced pathogenesis revealed by RNA-sequencing. PLoS Pathog 2010; 6:e1000834 [View Article][PubMed]
    [Google Scholar]
  8. Asplund MB, Coelho C, Cordero RJ, Martinez LR. Alcohol impairs J774.16 macrophage-like cell antimicrobial functions in Acinetobacter baumannii infection. Virulence 2013; 4:467–472 [View Article][PubMed]
    [Google Scholar]
  9. Gandhi JA, Ekhar VV, Asplund MB, Abdulkareem AF, Ahmadi M et al. Alcohol enhances Acinetobacter baumannii-associated pneumonia and systemic dissemination by impairing neutrophil antimicrobial activity in a murine model of infection. PLoS One 2014; 9:e95707 [View Article][PubMed]
    [Google Scholar]
  10. Anstey NM, Currie BJ, Hassell M, Palmer D, Dwyer B et al. Community-acquired bacteremic Acinetobacter pneumonia in tropical Australia is caused by diverse strains of Acinetobacter baumannii, with carriage in the throat in at-risk groups. J Clin Microbiol 2002; 40:685–686 [View Article][PubMed]
    [Google Scholar]
  11. Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL et al. Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 2002; 137:791–797 [View Article][PubMed]
    [Google Scholar]
  12. Sarovich DS. Microbial genome assembler pipeline. Available from https://github.com/dsarov/MGAP-Microbial-Genome-Assembler-Pipeline Accessed: June 17, 2017
  13. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article][PubMed]
    [Google Scholar]
  14. Sarovich DS, Price EP. SPANDx: a genomics pipeline for comparative analysis of large haploid whole genome re-sequencing datasets. BMC Res Notes 2014; 7:618 [View Article][PubMed]
    [Google Scholar]
  15. Weber BS, Ly PM, Irwin JN, Pukatzki S, Feldman MF. A multidrug resistance plasmid contains the molecular switch for type VI secretion in Acinetobacter baumannii. Proc Natl Acad Sci USA 2015; 112:9442–9447 [View Article][PubMed]
    [Google Scholar]
  16. PAUP* Available from http://paup.sc.fsu.edu/about.html Accessed: June 17, 2017
  17. Nguyen LT, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 2015; 32:268–274 [View Article][PubMed]
    [Google Scholar]
  18. Didelot X, Wilson DJ. ClonalFrameML: efficient inference of recombination in whole bacterial genomes. PLoS Comput Biol 2015; 11:e1004041 [View Article][PubMed]
    [Google Scholar]
  19. Suchard MA, Lemey P, Baele G, Ayres DL, Drummond AJ et al. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Virus Evol 2018; 4:vey016 [View Article][PubMed]
    [Google Scholar]
  20. Holt K, Kenyon JJ, Hamidian M, Schultz MB, Pickard DJ et al. Five decades of genome evolution in the globally distributed, extensively antibiotic-resistant Acinetobacter baumannii global clone 1. Microb Genom 2016; 2:e000052 [View Article][PubMed]
    [Google Scholar]
  21. Letunic I, Bork P. Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res 2016; 44:W242–W245 [View Article][PubMed]
    [Google Scholar]
  22. Chen L, Zheng D, Liu B, Yang J, Jin Q. VFDB 2016: hierarchical and refined dataset for big data analysis—10 years on. Nucleic Acids Research 2016; 44:D694–D697 [View Article]
    [Google Scholar]
  23. Richmond GE, Evans LP, Anderson MJ, Wand ME, Bonney LC et al. The Acinetobacter baumannii two-component system AdeRS regulates genes required for multidrug efflux, biofilm formation, and virulence in a strain-specific manner. mBio 2016; 7:e0043016 [View Article][PubMed]
    [Google Scholar]
  24. Weber BS, Miyata ST, Iwashkiw JA, Mortensen BL, Skaar EP et al. Genomic and functional analysis of the type VI secretion system in Acinetobacter. PLoS One 2013; 8:e55142 [View Article][PubMed]
    [Google Scholar]
  25. Inouye M, Dashnow H, Raven LA, Schultz MB, Pope BJ et al. SRST2: Rapid genomic surveillance for public health and hospital microbiology labs. Genome Med 2014; 6:90 [View Article][PubMed]
    [Google Scholar]
  26. Sahl JW, Caporaso JG, Rasko DA, Keim P. The large-scale blast score ratio (LS-BSR) pipeline: a method to rapidly compare genetic content between bacterial genomes. PeerJ 2014; 2:e332 [View Article][PubMed]
    [Google Scholar]
  27. Seemann T. Abricate. Available from https://github.com/tseemann/abricate Accessed: 11th February, 2018
  28. Bacterial Antimicrobial Resistance Reference Gene Database. Available from https://www.ncbi.nlm.nih.gov/bioproject/PRJNA313047 accessed: November 2, 2017
  29. Ou HY, 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 [View Article][PubMed]
    [Google Scholar]
  30. Schultz MB, Pham Thanh D, Tran do Hoan N, Wick RR, Ingle DJ et al. Repeated local emergence of carbapenem-resistant Acinetobacter baumannii in a single hospital ward. Microb Genom 2016; 2:e000050 [View Article][PubMed]
    [Google Scholar]
  31. Li H, Liu F, Zhang Y, Wang X, Zhao C et al. Evolution of carbapenem-resistant Acinetobacter baumannii revealed through whole-genome sequencing and comparative genomic analysis. Antimicrob Agents Chemother 2015; 59:1168–1176 [View Article][PubMed]
    [Google Scholar]
  32. 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 [View Article][PubMed]
    [Google Scholar]
  33. Tomaras AP, Flagler MJ, Dorsey CW, Gaddy JA, Actis LA. Characterization of a two-component regulatory system from Acinetobacter baumannii that controls biofilm formation and cellular morphology. Microbiology 2008; 154:3398–3409 [View Article][PubMed]
    [Google Scholar]
  34. Niu C, Clemmer KM, Bonomo RA, Rather PN. Isolation and characterization of an autoinducer synthase from Acinetobacter baumannii. J Bacteriol 2008; 190:3386–3392 [View Article][PubMed]
    [Google Scholar]
  35. 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 [View Article][PubMed]
    [Google Scholar]
  36. Russo TA, Luke NR, Beanan JM, Olson R, Sauberan SL et al. The K1 capsular polysaccharide of Acinetobacter baumannii strain 307-0294 is a major virulence factor. Infect Immun 2010; 78:3993–4000 [View Article][PubMed]
    [Google Scholar]
  37. Kenyon JJ, Hall RM. Variation in the complex carbohydrate biosynthesis loci of Acinetobacter baumannii genomes. PLoS One 2013; 8:e62160 [View Article][PubMed]
    [Google Scholar]
  38. Kenyon JJ, Marzaioli AM, Hall RM, de Castro C. Structure of the K12 capsule containing 5,7-di-N-acetylacinetaminic acid from Acinetobacter baumannii isolate D36. Glycobiology 2015; 25:881–887 [View Article][PubMed]
    [Google Scholar]
  39. 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 [View Article][PubMed]
    [Google Scholar]
  40. Vila J, Ruiz J, Goñi P, Jimenez de Anta T. Quinolone-resistance mutations in the topoisomerase IV parC gene of Acinetobacter baumannii. J Antimicrob Chemother 1997; 39:757–762 [View Article][PubMed]
    [Google Scholar]
  41. Vila J, Ruiz J, Goñi P, Marcos A, Jimenez de Anta T. Mutation in the gyrA gene of quinolone-resistant clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 1995; 39:1201–1203 [View Article][PubMed]
    [Google Scholar]
  42. Huovinen P. Resistance to trimethoprim-sulfamethoxazole. Clin Infect Dis 2001; 32:1608–1614 [View Article][PubMed]
    [Google Scholar]
  43. Akers KS, Mende K, Yun HC, Hospenthal DR, Beckius ML et al. Tetracycline susceptibility testing and resistance genes in isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus complex from a U.S. military hospital. Antimicrob Agents Chemother 2009; 53:2693–2695 [View Article][PubMed]
    [Google Scholar]
  44. Farrugia DN, Elbourne LD, Hassan KA, Eijkelkamp BA, Tetu SG et al. The complete genome and phenome of a community-acquired Acinetobacter baumannii. PLoS One 2013; 8:e58628 [View Article][PubMed]
    [Google Scholar]
  45. Eveillard M, Kempf M, Belmonte O, Pailhoriès H, Joly-Guillou ML. Reservoirs of Acinetobacter baumannii outside the hospital and potential involvement in emerging human community-acquired infections. Int J Infect Dis 2013; 17:e802e805 [View Article][PubMed]
    [Google Scholar]
  46. Pailhoriès H, Belmonte O, Kempf M, Lemarié C, Cuziat J et al. Diversity of Acinetobacter baumannii strains isolated in humans, companion animals, and the environment in Reunion Island: an exploratory study. Int J Infect Dis 2015; 37:64–69 [View Article][PubMed]
    [Google Scholar]
  47. Rafei R, Hamze M, Pailhoriès H, Eveillard M, Marsollier L et al. Extrahuman epidemiology of Acinetobacter baumannii in Lebanon. Appl Environ Microbiol 2015; 81:2359–2367 [View Article][PubMed]
    [Google Scholar]
  48. Zeana C, Larson E, Sahni J, Bayuga SJ, Wu F et al. The epidemiology of multidrug-resistant Acinetobacter baumannii: does the community represent a reservoir?. Infect Control Hosp Epidemiol 2003; 24:275–279 [View Article][PubMed]
    [Google Scholar]
  49. Murray CK, Yun HC, Griffith ME, Hospenthal DR, Tong MJ. Acinetobacter infection: what was the true impact during the Vietnam conflict?. Clin Infect Dis 2006; 43:383–384 [View Article][PubMed]
    [Google Scholar]
  50. Sebeny PJ, Riddle MS, Petersen K. Acinetobacter baumannii skin and soft-tissue infection associated with war trauma. Clin Infect Dis 2008; 47:444–449 [View Article][PubMed]
    [Google Scholar]
  51. Elston JW, Bannan CL, Chih DT, Boutlis CS. Acinetobacter spp. in gunshot injuries. Emerg Infect Dis 2008; 14:178–180 [View Article][PubMed]
    [Google Scholar]
  52. Maegele M, Gregor S, Steinhausen E, Bouillon B, Heiss MM et al. The long-distance tertiary air transfer and care of tsunami victims: injury pattern and microbiological and psychological aspects. Crit Care Med 2005; 33:1136–1140 [View Article][PubMed]
    [Google Scholar]
  53. Popovich KJ, Snitkin ES, Hota B, Green SJ, Pirani A et al. Genomic and epidemiological evidence for community origins of hospital-onset methicillin-resistant Staphylococcus aureus bloodstream infections. J Infect Dis 2017; 215:1640–1647 [View Article][PubMed]
    [Google Scholar]
  54. Chen C-T, Wang Y-C, Kuo S-C, Shih F-H, Chen T-L et al. Community-acquired bloodstream infections caused by Acinetobacter baumannii: A matched case–control study. J Microbiol Immunol Infect 2018; 51:629–635 [View Article]
    [Google Scholar]
  55. Harris G, Kuo Lee R, Lam CK, Kanzaki G, Patel GB et al. A mouse model of Acinetobacter baumannii-associated pneumonia using a clinically isolated hypervirulent strain. Antimicrob Agents Chemother 2013; 57:3601–3613 [View Article][PubMed]
    [Google Scholar]
  56. 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 [View Article][PubMed]
    [Google Scholar]
  57. Cooper RM, Tsimring L, Hasty J. Inter-species population dynamics enhance microbial horizontal gene transfer and spread of antibiotic resistance. Elife 2017; 6: [View Article][PubMed]
    [Google Scholar]
  58. Vinogradov E, Maclean L, Xu HH, Chen W. The structure of the polysaccharide isolated from Acinetobacter baumannii strain LAC-4. Carbohydr Res 2014; 390:42–45 [View Article][PubMed]
    [Google Scholar]
  59. Zhou K, Tang X, Wang L, Guo Z, Xiao S et al. An emerging clone (ST457) of Acinetobacter baumannii clonal complex 92 with enhanced virulence and increasing endemicity in South China. Clin Infect Dis 2018; 67:S179–S188 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000258
Loading
/content/journal/mgen/10.1099/mgen.0.000258
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF

Supplementary File 2

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error