The Acinetobacter baumannii Mla system and glycerophospholipid transport to the outer membrane
The Acinetobacter baumannii Mla system and glycerophospholipid transport to the outer membrane
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DOI：
10.7554/elife.40171
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发表时间：
2019-01-14
期刊：
影响因子：
7.7
通讯作者：
Miller, Samuel I.
中科院分区：
文献类型：
--
作者：
Kamischke, Cassandra;Fan, Junping;Miller, Samuel I.
革兰氏阴性菌的外膜（OM）是一种选择性渗透屏障，允许必需营养素进入，同时排除有毒化合物，包括抗生素。OM是不对称的，包含脂多糖（LPS）或脂寡糖（LOS）的外小叶和甘油磷脂（GPL）的内小叶。我们筛选了鲍曼不动杆菌转座子突变体，并鉴定了一些OM缺陷突变体，包括与大肠杆菌Mla系统同源的ABC转运系统。杆菌我们进一步表明，这种机会主义的，耐药的病原体使用这种多组分蛋白质复合物和ATP水解在内膜，以促进GPL出口到OM。Mla系统在革兰氏阴性菌中的广泛保守性表明该系统可能在OM生物发生中起保守作用。Mla系统对鲍曼不动杆菌OM完整性和抗生素敏感性的重要性表明其组分可作为新的抗菌治疗靶点。
The outer membrane (OM) of Gram-negative bacteria serves as a selective permeability barrier that allows entry of essential nutrients while excluding toxic compounds, including antibiotics. The OM is asymmetric and contains an outer leaflet of lipopolysaccharides (LPS) or lipooligosaccharides (LOS) and an inner leaflet of glycerophospholipids (GPL). We screened Acinetobacter baumannii transposon mutants and identified a number of mutants with OM defects, including an ABC transporter system homologous to the Mla system in E. coli. We further show that this opportunistic, antibiotic-resistant pathogen uses this multicomponent protein complex and ATP hydrolysis at the inner membrane to promote GPL export to the OM. The broad conservation of the Mla system in Gram-negative bacteria suggests the system may play a conserved role in OM biogenesis. The importance of the Mla system to Acinetobacter baumannii OM integrity and antibiotic sensitivity suggests that its components may serve as new antimicrobial therapeutic targets.