The antimicrobial peptide-sensing system aps of Staphylococcus aureus
The antimicrobial peptide-sensing system aps of Staphylococcus aureus
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DOI：
10.1111/j.1365-2958.2007.05986.x
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发表时间：
2007-12-01
影响因子：
3.6
通讯作者：
Otto, Michael
中科院分区：
文献类型：
--
作者：
Li, Min;Cha, David J.;Otto, Michael
金黄色葡萄球菌是由高毒力耐甲氧西林菌株（CA-MRSA）引起的医院相关感染以及最近的社区相关感染的主要原因。S.金黄色葡萄球菌在人类宿主中的存活主要由逃避抗微生物肽（AMP）攻击的能力和先天宿主防御的其它机制决定。在这里，我们表明，AMP通过aps AMP传感器/调节器系统，包括（i）磷壁酸的D-丙氨酰化，（ii）在细菌膜中掺入赖氨酰磷脂酰甘油，并伴随着赖氨酸生物合成的增加，以及（iii）推定的AMP转运系统，如vraFG转运蛋白，我们证明了AMP耐药的功能。与S. epidermidis，诱导S.金黄色葡萄球菌是AMP选择性的，这是由于ApsS传感器蛋白的AMP结合环的结构差异。最后，利用小鼠感染模型，我们证明了aps调控系统在S。金黄色葡萄球菌感染。这项研究表明，虽然在AMP-aps相互作用中存在显着的种间差异，但AMP传感器系统aps在促进重要人类病原体S的临床相关菌株对各种AMP的抗性方面是功能性的和有效的。金黄色。
Staphylococcus aureus is a leading cause of hospital-associated and, more recently, community-associated infections caused by highly virulent methicillin-resistant strains (CA-MRSA). S. aureus survival in the human host is largely defined by the ability to evade attacks by antimicrobial peptides (AMPs) and other mechanisms of innate host defence. Here we show that AMPs induce resistance mechanisms in CA-MRSA via the aps AMP sensor/regulator system, including (i) the D-alanylation of teichoic acids, (ii) the incorporation of lysylphosphatidylglycerol in the bacterial membrane and a concomitant increase in lysine biosynthesis, and (iii) putative AMP transport systems such as the vraFG transporter, for which we demonstrate a function in AMP resistance. In contrast to the aps system of S. epidermidis, induction of the aps response in S. aureus was AMP-selective due to structural differences in the AMP binding loop of the ApsS sensor protein. Finally, using a murine infection model, we demonstrate the importance of the aps regulatory system in S. aureus infection. This study shows that while significant interspecies differences exist in the AMP-aps interaction, the AMP sensor system aps is functional and efficient in promoting resistance to a variety of AMPs in a clinically relevant strain of the important human pathogen S. aureus.