ISAba1-dependent overexpression of eptA in clinical strains of Acinetobacter baumannii resistant to colistin

Author:

Potron Anaïs12ORCID,Vuillemenot Jean-Baptiste2,Puja Hélène2,Triponney Pauline1,Bour Maxime1,Valot Benoit2,Amara Marlène3,Cavalié Laurent4,Bernard Christine5,Parmeland Laurence6,Reibel Florence7,Larrouy-Maumus Gerald8,Dortet Laurent910,Bonnin Rémy A910ORCID,Plésiat Patrick12

Affiliation:

1. French National Reference Centre for Antibiotic Resistance, University Hospital of Besançon, Besançon, France

2. UMR6249, CNRS Chrono-Environnement, Franche-Comté University, Besançon, France

3. Hospital of Versailles, Le Chesnay, France

4. University Hospital of Toulouse, Toulouse, France

5. Grand Hôpital de l’Est Parisien, Jossigny, France

6. Saint-Joseph Saint-Luc Hospital, Lyon, France

7. Groupe Hospitalier Nord Essonne, Longjumeau, France

8. MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, UK

9. EA7361 ‘Structure, Dynamic, Function and Expression of Broad Spectrum β-Lactamases’, Paris-Sud University, LabEx Lermit, Faculty of Medicine, Le Kremlin-Bicêtre, France

10. French National Reference Centre for Antibiotic Resistance, Associate Laboratory, Le Kremlin-Bicêtre, France

Abstract

AbstractBackgroundColistin resistance in Acinetobacter baumannii often results from mutational activation of the two-component system PmrAB and subsequent addition of phospho-ethanolamine (pEtN) to lipooligosaccharide by up-regulated pEtN transferase PmrC.ObjectivesTo characterize mechanisms of colistin resistance independent of PmrCAB in A. baumannii.MethodsTwenty-seven colistin-resistant A. baumannii were collected from 2012 to 2018. Analysis of operon pmrCAB was performed by PCR and sequencing. Seven strains were investigated further by WGS and whole-genome MLST (wgMLST).ResultsSeven out of the 27 selected isolates were found to overexpress eptA, a gene homologous to pmrC, likely as a consequence of upstream insertion of an ISAba1 element. Insertion sites of ISAba1 were mapped 13, 18 and 156 bp ahead of the start codon of eptA in five strains, one strain and one strain, respectively. The finding that the isolates did not cluster together when compared by wgMLST analysis supports the notion that distinct insertion events occurred in close, but different, genetic backgrounds.ConclusionsActivation of eptA and subsequent addition of pEtN to the cell surface represents a novel mechanism of resistance to colistin in A. baumannii.

Funder

French Ministry of Health

Santé publique France agency

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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