Dissecting Colistin Resistance Mechanisms in Extensively Drug-Resistant Acinetobacter baumannii Clinical Isolates

Author:

Trebosc Vincent12,Gartenmann Sarah1,Tötzl Marcus1,Lucchini Valentina12,Schellhorn Birgit1,Pieren Michel1,Lociuro Sergio1,Gitzinger Marc1,Tigges Marcel1,Bumann Dirk2,Kemmer Christian1

Affiliation:

1. BioVersys AG, Basel, Switzerland

2. Biozentrum, University of Basel, Basel, Switzerland

Abstract

The discovery of antibiotics revolutionized modern medicine and enabled us to cure previously deadly bacterial infections. However, a progressive increase in antibiotic resistance rates is a major and global threat for our health care system. Colistin represents one of our last-resort antibiotics that is still active against most Gram-negative bacterial pathogens, but increasing resistance is reported worldwide, in particular due to the plasmid-encoded protein MCR-1 present in pathogens such as Escherichia coli and Klebsiella pneumoniae . Here, we showed that colistin resistance in A. baumannii , a top-priority pathogen causing deadly nosocomial infections, is mediated through different avenues that result in increased activity of homologous phosphoethanolamine (PetN) transferases. Considering that MCR-1 is also a PetN transferase, our findings indicate that PetN transferases might be the Achilles heel of superbugs and that direct targeting of them may have the potential to preserve the activity of polymyxin antibiotics.

Funder

European Union Horizon 2020 Research and Innovation Programme

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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