Colistin Resistance in Acinetobacter baumannii MDR-ZJ06 Revealed by a Multiomics Approach.

Colistin Resistance in Acinetobacter baumannii MDR-ZJ06 Revealed by a Multiomics Approach.
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多组学方法揭示鲍曼不动杆菌 MDR-ZJ06 中的粘菌素耐药性

DOI:
10.3389/fcimb.2017.00045
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发表时间:
2017
影响因子:
5.7
通讯作者:
Yu Y
Yu Y
中科院分区:
医学2区
文献类型:
--
作者:
Hua X;Liu L;Fang Y;Shi Q;Li X;Chen Q;Shi K;Jiang Y;Zhou H;Yu Y

文献摘要

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鲍氏不动杆菌由于其获得对大多数当前可用的抗生素的抗性的能力而成为重要的机会致病菌。多粘菌素通常被认为是治疗多重耐药A。鲍曼不动杆菌(MDRAB)。然而,粘菌素耐药的A.鲍曼不动杆菌菌株最近已有报道。探讨多重耐药A.鲍曼不动杆菌对粘菌素耐药的反应,我们比较了鲍曼不动杆菌的基因组、转录和蛋白质组谱。鲍曼不动杆菌MDR-ZJ 06对诱导的粘菌素耐药菌株ZJ 06 - 200 P5 -1的抗性。基因组分析表明,lpxC被ISAba 1插入失活,导致LPS丢失。转录分析表明,粘菌素耐药菌株调节其代谢。蛋白质组学分析表明RND外排泵系统表达增加,FabZ和β-内酰胺酶表达下调。这些变化被认为是对LPS损失的反应。总之,lpxC突变不仅建立了粘菌素抗性,而且改变了整体基因表达。
Acinetobacter baumannii has emerged as an important opportunistic pathogen due to its ability to acquire resistance to most currently available antibiotics. Colistin is often considered as the last line of therapy for infections caused by multidrug-resistant A. baumannii (MDRAB). However, colistin-resistant A. baumannii strain has recently been reported. To explore how multiple drug-resistant A. baumannii responded to colistin resistance, we compared the genomic, transcriptional and proteomic profile of A. baumannii MDR-ZJ06 to the induced colistin-resistant strain ZJ06-200P5-1. Genomic analysis showed that lpxC was inactivated by ISAba1 insertion, leading to LPS loss. Transcriptional analysis demonstrated that the colistin-resistant strain regulated its metabolism. Proteomic analysis suggested increased expression of the RND efflux pump system and down-regulation of FabZ and β-lactamase. These alterations were believed to be response to LPS loss. In summary, the lpxC mutation not only established colistin resistance but also altered global gene expression.