Colistin Resistance in Acinetobacter baumannii Is Mediated by Complete Loss of Lipopolysaccharide Production
Colistin Resistance in Acinetobacter baumannii Is Mediated by Complete Loss of Lipopolysaccharide Production
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DOI：
10.1128/aac.00834-10
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发表时间：
2010-12-01
影响因子：
4.9
通讯作者：
Boyce, John D.
中科院分区：
文献类型：
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作者：
Moffatt, Jennifer H.;Harper, Marina;Boyce, John D.
由多重耐药（MDR）革兰氏阴性菌引起的感染代表了主要的全球健康问题。多粘菌素类抗生素如粘菌素已重新出现，作为有效的最后手段抗微生物剂，用于对抗MDR革兰氏阴性病原体，包括鲍曼不动杆菌。在这里，我们表明，A.鲍曼不动杆菌可通过完全丧失最初的结合靶（脂多糖（LPS）的脂质A组分）而迅速产生对多粘菌素抗生素的抗性，长期以来，脂多糖被认为是革兰氏阴性菌生存所必需的。我们确定了13个独立的粘菌素耐药的A。鲍曼不动杆菌型菌株ATCC 19606中的突变，并显示所有突变都包含在脂质A生物合成途径的前三个基因之一内：lpxA、lpxC和lpxD。所有这些突变导致LPS产生的完全丧失。此外，我们发现LPS的损失发生在粘菌素耐药的临床分离的A。鲍曼不动杆菌。这是第一次报告的自发发生，脂多糖缺乏，革兰氏阴性细菌。
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.