Wall teichoic acid deficiency in Staphylococcus aureus confers selective resistance to mammalian group IIA phospholipase A2 and human p-defensin 3
Wall teichoic acid deficiency in Staphylococcus aureus confers selective resistance to mammalian group IIA phospholipase A2 and human p-defensin 3
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DOI：
10.1128/iai.01705-07
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发表时间：
2008-05-01
影响因子：
3.1
通讯作者：
Weiss, Jerrold P.
中科院分区：
文献类型：
--
作者：
Koprivnjak, Tomaz;Weidenmaier, Christopher;Weiss, Jerrold P.
壁磷壁酸（WTA）和膜脂磷壁酸（LTA）是金黄色葡萄球菌包膜中主要的聚阴离子聚合物。在S。金黄色葡萄球菌在噬菌体附着和细菌粘附到某些宿主细胞中起重要作用，这表明WTA暴露在细胞表面上，并且还可以为阳离子抗菌肽和蛋白质（CAMP）提供必要的结合位点。高阳离子哺乳动物IIA族磷脂酶A（2）（gIIA PLA（2））杀死S.通过依赖于初始静电相互作用、细胞壁渗透、膜磷脂（PL）降解和自溶素活化的作用，以纳摩尔浓度对金黄色葡萄球菌进行细胞内给药。S.缺乏WTA的金黄色葡萄球菌对PL降解和gIIA PLA 2和CAMP人P-防御素3（HBD-3）的杀伤的抗性高100倍，但对其他CAMP（如Magainin 11酰胺、hNP 1 -3、LL-37和乳铁蛋白）具有野生型（wt）的敏感性。相反，野生型和tagO型S.金黄色葡萄球菌或gIIA PLA 2与wt和tagO菌株的结合。扫描和透射电子显微镜显示，在S。金黄色葡萄球菌tagO突变体，这可能是导致结合的gIIA PLA 2和HBD-3对tagO突变体的活性降低的原因。综上所述，S.金黄色葡萄球菌引起细菌对gIIA PIA（2）和HBD-3的抗性的选择性增加，前者显然是通过减少结合到细菌膜的抗菌酶的接近和/或活性。
Wall teichoic acids (WTAs) and membrane lipoteichoic acids (LTAs) are the major polyanionic polymers in the envelope of Staphylococcus aureus. WTAs in S. aureus play an important role in bacteriophage attachment and bacterial adherence to certain host cells, suggesting that WTAs are exposed on the cell surface and could also provide necessary binding sites for cationic antimicrobial peptides and proteins (CAMPs). Highly cationic mammalian group IIA phospholipase A(2) (gIIA PLA(2)) kills S. aureus at nanomolar concentrations by an action(s) that depends on initial electrostatic interactions, cell wall penetration, membrane phospholipid (PL) degradation, and activation of autolysins. A tagO mutant of S. aureus that lacks WTA is up to 100-fold more resistant to PL degradation and killing by gIIA PLA2 and CAMP human P-defensin 3 (HBD-3) but has the sensitivity of the wild type (wt) to other CAMPs, such as Magainin 11 amide, hNP1-3, LL-37, and lactoferrin. In contrast, there is little or no difference in either gIIA PLA2 activity toward cell wall-depleted protoplasts of the wt and tagO strains of S. aureus or in binding of gIIA PLA2 to wt and tagO strains. Scanning and transmission electron microscopy reveal increased surface protrusions in the S. aureus tagO mutant that might account for reduced activity of bound gIIA PLA2 and HBD-3 toward the tagO mutant. In summary, the absence of WTA in S. aureus causes a selective increase in bacterial resistance to gIIA PIA(2) and HBD-3, the former apparently by reducing access and/or activity of bound antibacterial enzyme to the bacterial membrane.