Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production

Jennifer H Moffatt, Marina Harper, Paul F Harrison, John DF Hale, Evgeny Vinogradov, Torsten Seemann, Rebekah M Henry, Bethany A Crane, Frank St Michael, Andrew D Cox, Ben Adler, Roger L Nation, Jian Li, John Dallas Boyce

Research output: Contribution to journalArticleResearchpeer-review

383 Citations (Scopus)

Abstract

Infections caused by multi-drug resistant (MDR) Gram-negative bacteria represent a major global health problem. Polymyxin antibiotics such as colistin have resurfaced as effective last-resort antimicrobials for use against MDR Gram-negative pathogens, including Acinetobacter baumannii. Here we show that A. baumannii can rapidly develop resistance to polymyxin antibiotics by complete loss of the initial binding target, the lipid A component of lipopolysaccharide (LPS), which has long been considered to be essential for the viability of Gram-negative bacteria. We characterised thirteen independent colistin-resistant derivatives of the A. baumannii type strain ATCC 19606 and showed that all contained mutations within one of the first three genes of the lipid A biosynthesis pathway; lpxA, lpxC and lpxD. These mutations all resulted in the complete loss of LPS production. Furthermore, we showed that loss of LPS occurs in a colistin-resistant clinical isolate of A. baumannii. This is the first report of a spontaneously occurring, lipopolysaccharide-deficient, Gram-negative bacterium.
Original languageEnglish
Pages (from-to)4971 - 4977
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume54
Issue number12
DOIs
Publication statusPublished - 2010

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