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Antimicrob Agents Chemother. 2010 Dec;54(12):4971-7. doi: 10.1128/AAC.00834-10. Epub 2010 Sep 20.

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

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  • 1Department of Microbiology, Building 76, Monash University, Clayton, Victoria 3800, Australia.

Abstract

Infections caused by multidrug-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 characterized 13 independent colistin-resistant derivatives of 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. All of these mutations 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.

PMID:
20855724
[PubMed - indexed for MEDLINE]
PMCID:
PMC2981238
Free PMC Article
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