Colistin Resistance in <i>Acinetobacter baumannii</i> Is Mediated by Complete Loss of Lipopolysaccharide Production

Antimicrobial Agents and Chemotherapy - Tập 54 Số 12 - Trang 4971-4977 - 2010
Jennifer H. Moffatt1, Marina Harper2,3, Paul F. Harrison4, John K. Hale5, Evgeny Vinogradov6, Torsten Seemann4, Rebekah Henry3, Bethany Crane3, Frank St. Michael6, Andrew D. Cox6, Ben Adler2,4, Roger L. Nation5, Jian Li5, John D. Boyce2,3
1Department of Microbiology, Building 76, Monash University, Clayton, Victoria 3800, Australia.
2Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria, Australia
3Department of Microbiology, Monash University, Clayton, Victoria, Australia
4Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria, Australia
5Facility for Anti-Infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Clayton, Victoria, Australia
6Institute for Biological Sciences, National Research Council, Ottawa, Ontario Canada

Tóm tắt

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.

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Antimicrobial Agents and Chemotherapy

Tập 54 Số 12

4971-4977

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