Phylogenomics of colistin-susceptible and resistant XDR Acinetobacter baumannii

Mustapha M. Mustapha, Bin Li, Marissa P. Pacey, Roberta T. Mettus, Christi L. McElheny, Christopher W. Marshall, Robert K. Ernst, Vaughn S. Cooper, Yohei Doi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Acinetobacter baumannii is a healthcare-associated pathogen with high rates of carbapenem resistance. Colistin is now routinely used for treatment of infections by this pathogen. However, colistin use has been associated with development of resistance to this agent. Objectives: To elucidate the phylogenomics of colistin-susceptible and -resistant A. baumannii strain pairs from a cohort of hospitalized patients at a tertiary medical centre in the USA. Methods: WGS data from 21 pairs of colistin-susceptible and -resistant, XDR clinical strains were obtained and compared using phylogeny of aligned genome sequences, assessment of pairwise SNP differences and gene content. Results: Fourteen patients had colistin-resistant strains that were highly genetically related to their own original susceptible strain with a median pairwise SNP distance of 5.5 (range 1–40 SNPs), while seven other strain pairs were divergent with 84 SNP differences. In addition, several strains from different patients formed distinct clusters on the phylogeny in keeping with closely linked transmission chains. The majority of colistin-resistant strains contained non-synonymous mutations within the pmrAB locus suggesting a central role for pmrAB mutations in colistin resistance. Excellent genotype–phenotype correlation was also observed for carbapenems, aminoglycosides and tetracyclines. Conclusions: The findings suggest that colistin resistance in the clinical setting arises through both in vivo evolution from colistin-susceptible strains and reinfection by unrelated colistin-resistant strains, the latter of which may involve patient-to-patient transmission.

Original languageEnglish
Pages (from-to)2952-2959
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume73
Issue number11
DOIs
Publication statusPublished - 01-01-2018

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Colistin
Acinetobacter baumannii
Single Nucleotide Polymorphism
Carbapenems
Phylogeny
Tetracyclines
Mutation
Aminoglycosides
Genome
Delivery of Health Care

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Mustapha, M. M., Li, B., Pacey, M. P., Mettus, R. T., McElheny, C. L., Marshall, C. W., ... Doi, Y. (2018). Phylogenomics of colistin-susceptible and resistant XDR Acinetobacter baumannii. Journal of Antimicrobial Chemotherapy, 73(11), 2952-2959. https://doi.org/10.1093/jac/dky290
Mustapha, Mustapha M. ; Li, Bin ; Pacey, Marissa P. ; Mettus, Roberta T. ; McElheny, Christi L. ; Marshall, Christopher W. ; Ernst, Robert K. ; Cooper, Vaughn S. ; Doi, Yohei. / Phylogenomics of colistin-susceptible and resistant XDR Acinetobacter baumannii. In: Journal of Antimicrobial Chemotherapy. 2018 ; Vol. 73, No. 11. pp. 2952-2959.
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Mustapha, MM, Li, B, Pacey, MP, Mettus, RT, McElheny, CL, Marshall, CW, Ernst, RK, Cooper, VS & Doi, Y 2018, 'Phylogenomics of colistin-susceptible and resistant XDR Acinetobacter baumannii', Journal of Antimicrobial Chemotherapy, vol. 73, no. 11, pp. 2952-2959. https://doi.org/10.1093/jac/dky290

Phylogenomics of colistin-susceptible and resistant XDR Acinetobacter baumannii. / Mustapha, Mustapha M.; Li, Bin; Pacey, Marissa P.; Mettus, Roberta T.; McElheny, Christi L.; Marshall, Christopher W.; Ernst, Robert K.; Cooper, Vaughn S.; Doi, Yohei.

In: Journal of Antimicrobial Chemotherapy, Vol. 73, No. 11, 01.01.2018, p. 2952-2959.

Research output: Contribution to journalArticle

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T1 - Phylogenomics of colistin-susceptible and resistant XDR Acinetobacter baumannii

AU - Mustapha, Mustapha M.

AU - Li, Bin

AU - Pacey, Marissa P.

AU - Mettus, Roberta T.

AU - McElheny, Christi L.

AU - Marshall, Christopher W.

AU - Ernst, Robert K.

AU - Cooper, Vaughn S.

AU - Doi, Yohei

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Acinetobacter baumannii is a healthcare-associated pathogen with high rates of carbapenem resistance. Colistin is now routinely used for treatment of infections by this pathogen. However, colistin use has been associated with development of resistance to this agent. Objectives: To elucidate the phylogenomics of colistin-susceptible and -resistant A. baumannii strain pairs from a cohort of hospitalized patients at a tertiary medical centre in the USA. Methods: WGS data from 21 pairs of colistin-susceptible and -resistant, XDR clinical strains were obtained and compared using phylogeny of aligned genome sequences, assessment of pairwise SNP differences and gene content. Results: Fourteen patients had colistin-resistant strains that were highly genetically related to their own original susceptible strain with a median pairwise SNP distance of 5.5 (range 1–40 SNPs), while seven other strain pairs were divergent with 84 SNP differences. In addition, several strains from different patients formed distinct clusters on the phylogeny in keeping with closely linked transmission chains. The majority of colistin-resistant strains contained non-synonymous mutations within the pmrAB locus suggesting a central role for pmrAB mutations in colistin resistance. Excellent genotype–phenotype correlation was also observed for carbapenems, aminoglycosides and tetracyclines. Conclusions: The findings suggest that colistin resistance in the clinical setting arises through both in vivo evolution from colistin-susceptible strains and reinfection by unrelated colistin-resistant strains, the latter of which may involve patient-to-patient transmission.

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Mustapha MM, Li B, Pacey MP, Mettus RT, McElheny CL, Marshall CW et al. Phylogenomics of colistin-susceptible and resistant XDR Acinetobacter baumannii. Journal of Antimicrobial Chemotherapy. 2018 Jan 1;73(11):2952-2959. https://doi.org/10.1093/jac/dky290