Concepedia

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

Jennifer H. Moffatt, Marina Harper, Paul F. Harrison, John Hale, Evgeny Vinogradov, Torsten Seemann, Rebekah Henry, Bethany Crane, Frank St. Michael, Andrew D. Cox,

Antimicrobial Agents and Chemotherapy · 2010 · 792 citations · 30 references

DOI

TL;DR

Multidrug‑resistant Gram‑negative bacterial infections pose a major global health threat, and polymyxins such as colistin have become the last‑resort antibiotics for pathogens like Acinetobacter baumannii. We examined 13 colistin‑resistant A. baumannii ATCC 19606 derivatives and found that each harbored mutations in one of the first three genes (lpxA, lpxC, lpxD) of the lipid‑A biosynthesis pathway.

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.