Mechanisms of daptomycin resistance in Staphylococcus aureus: role of the cell membrane and cell wall.
Mechanisms of daptomycin resistance in Staphylococcus aureus: role of the cell membrane and cell wall.
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DOI：
10.1111/j.1749-6632.2012.06819.x
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发表时间：
2013-01
影响因子：
5.2
通讯作者：
Sahl HG
中科院分区：
文献类型：
--
作者：
Bayer AS;Schneider T;Sahl HG
杀菌、细胞膜靶向脂肽抗生素达托霉素（DAP）是治疗侵袭性金黄色葡萄球菌感染的重要药物。然而，最近有许多报道称，在使用该药物治疗期间发生了达托霉素耐药性（DAP-R）。DAP-R在S.金黄色葡萄球菌似乎是相当多样的。DAP-R菌株通常在多肽抗性因子基因（mprF）和yycFGHI操纵子的yycFG组分中表现出单核苷酸多态性的进行性积累。这两个基因座都参与关键细胞膜（CM）事件，mprF负责合成和外CM易位的带正电荷的磷脂，赖氨酰磷脂酰甘油（L-PG），而yyc操纵子参与的一般性反应，如抗微生物剂的压力。此外，在DAP-R菌株中还发现了CM的其他扰动，包括：CM顺序的极端;对CM去极化和透化的抗性;以及DAP表面结合减少。此外，细胞壁（CW）的修饰似乎也有助于DAP-R，包括dlt操纵子（参与CW磷壁酸的D-丙氨酰化）的表达增强和CW进行性增厚。
The bactericidal, cell membrane-targeting lipopeptide antibiotic daptomycin (DAP) is an important agent in treating invasive Staphylococcus aureus infections. However, there have been numerous recent reports of development of daptomycin-resistance (DAP-R) during therapy with this agent. The mechanisms of DAP-R in S. aureus appear to be quite diverse. DAP-R strains often exhibit progressive accumulation of single nucleotide polymorphisms in the multipeptide resistance factor gene (mprF) and the yycFG components of the yycFGHI operon. Both loci are involved in key cell membrane (CM) events, with mprF being responsible for the synthesis and outer CM translocation of the positively-charged phospholipid, lysyl-phosphotidylglycerol (L-PG), while the yyc operon is involved in the generalized response to stressors such as antimicrobials. In addition, other perturbations of the CM have been identified in DAP-R strains including: extremes in CM order; resistance to CM depolarization and permeabilization; and reduced surface binding of DAP. Moreover, modifications of the cell wall (CW) appear to also contribute to DAP-R, including enhanced expression of the dlt operon (involved in D-alanylation of CW teichoic acids) and progressive CW thickening.
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