Inherent colistin resistance in Genogroups of the Enterobacter cloacae complex: epidemiological, genetic and biochemical analysis from the BSAC Resistance Surveillance Programme

Shazad Mushtaq, Rosy Reynolds, Michael C Gilmore, Olobukola Esho, Rachel Adkin, Immaculada García-Romero, Aiysha Chaudhry, Carolyne Horner, Toby Bartholomew, Miguel A Valvano, Magdalena Dry, John Murray, Bruno Pichon, David M Livermore*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

Abstract

Background Polymyxins have re-entered use against problem Gram-negative bacteria. Resistance rates are uncertain, with estimates confounded by selective testing. Methods The BSAC Resistance Surveillance Programme has routinely tested colistin since 2010; we reviewed data up to 2017 for relevant Enterobacterales (n = 10 914). Unexpectedly frequent resistance was seen among the Enterobacter cloacae complex isolates (n = 1749); for these, we investigated relationships to species, genome, carbon source utilization and LPS structure. Results Annual colistin resistance rates among E. cloacae complex isolates were 4.4%–20%, with a rising trend among bloodstream organisms; in contrast, annual rates for Escherichia coli and Klebsiella spp. (including K. aerogenes) generally remained <2%. WGS split the E. cloacae complex isolates into seven genogroup clusters, designated A–G. Among isolates assigned to genogroups A–D, 47/50 sequenced were colistin resistant, and many of those belonging to genogroups A–C identified as E. asburiae. Isolates belonging to genogroups E–G consistently identified as E. cloacae and were rarely (only 3/45 representatives sequenced) colistin resistant. Genogroups F and G, the predominant colistin-susceptible clusters, were metabolically distinct from other clusters, notably regarding utilization or not of L-fucose, formic acid, D-serine, adonitol, myo-inositol, L-lyxose and polysorbates. LPS from resistant organisms grown without colistin pressure lacked substitutions with 4-amino-arabinose or ethanolamine but was more structurally complex, with more molecular species present. Conclusions Colistin resistance is frequent in the E. cloacae complex and increasing among bloodstream isolates. It is associated with: (i) particular genomic and metabolic clusters; (ii) identification as E. asburiae; and (iii) with more complex LPS architectures.
Original languageEnglish
Article numberdkaa201
Number of pages10
JournalJournal of Antimicrobial Chemotherapy
DOIs
Publication statusPublished - 8 Jun 2020

Keywords

  • colistin
  • enterobacter cloacae
  • surveillance program

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