Cell-wall determinants of the bactericidal action of group IIA phospholipase A2 against Gram-positive bacteria
Cell-wall determinants of the bactericidal action of group IIA phospholipase A2 against Gram-positive bacteria
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DOI：
10.1172/jci5468
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发表时间：
1999-03-01
影响因子：
15.9
通讯作者：
Weiss, J
中科院分区：
文献类型：
--
作者：
Foreman-Wykert, AK;Weinrauch, Y;Weiss, J
我们以前已经证明，IIA族磷脂酶A（2）（PLA（2））负责炎症液体对许多革兰氏阳性细菌的有效杀菌活性。为了发挥其抗菌活性，这种PLA 2必须首先结合并穿过细菌细胞壁，以产生杀死细菌所需的膜磷脂（PL）的广泛降解。在这项研究中，我们已经检查了细胞壁的性质，可能会决定的效力IIA族PLA（2）的行动。通过营养剥夺或抑菌抗生素抑制细菌生长可逆地增加了细菌对PLA（2）触发的PL降解和杀伤的抗性。相反，用亚抑制剂量的β-内酰胺类抗生素预处理金黄色葡萄球菌或屎肠球菌，在加入PLA后，PL降解和/或细菌杀灭的速率和程度增加（2）。同源野生型（lyt（+））和自溶缺陷型（lyt（-））菌株。金黄色葡萄球菌对PLA（2）的磷脂分解作用同样敏感，但lyt（+）菌株的杀伤和溶解作用更强。因此，细胞壁交联和/或自溶活性的变化可以通过影响酶进入膜PL或通过将大量PL降解偶联到自溶素依赖性杀伤和细菌裂解或两者来调节PLA（2）的作用。总之，这些发现表明，参与细胞生长的细菌包膜位点可能代表IIA族PLA（2）攻击革兰氏阳性菌的作用和细胞毒性后果的优先位点。
We have shown previously that a group IIA phospholipase A(2) (PLA(2)) is responsible for the potent bactericidal activity of inflammatory fluids against many Gram-positive bacteria. To exert its antibacterial activity, this PLA2 must first bind and traverse the bacterial cell wall to produce the extensive degradation of membrane phospholipids (PL) required for bacterial killing. In this study, we have examined the properties of the cell-wall that may determine the potency of group IIA PLA(2) action. Inhibition of bacterial growth by nutrient deprivation or a bacteriostatic antibiotic reversibly increased bacterial resistance to PLA(2)-triggered PL degradation and killing. Conversely, pretreatment of Staphylococcus aureus or Enterococcus faecium with subinhibitory doses of beta-lactam antibiotics increased the rate and extent of PL degradation and/or bacterial killing after addition of PLA(2). Isogenic wild-type (lyt(+)) and autolysis-deficient (lyt(-)) strains of S. aureus were equally sensitive to the phospholipolytic action of PLA(2), but killing and lysis was much greater in the lyt(+) strain. Thus, changes in cell-wall cross-linking and/or autolytic activity can modulate PLA(2) action either by affecting enzyme access to membrane PL or by the coupling of massive PL degradation to autolysin-dependent killing and bacterial lysis or both. Taken together, these findings suggest that the bacterial envelope sites engaged in cell growth may represent preferential sites for the action and cytotoxic consequences of group IIA PLA(2) attack against Gram-positive bacteria.