Enhanced production of phospholipase C and perfringolysin O (alpha and theta toxins) in a gatifloxacin-resistant strain of Clostridium perfringens.
Enhanced production of phospholipase C and perfringolysin O (alpha and theta toxins) in a gatifloxacin-resistant strain of Clostridium perfringens.
复制标题
产气荚膜梭菌耐加替沙星菌株中磷脂酶 C 和产气荚膜溶血素 O（α 和 θ 毒素）的产量增加。
DOI：
10.1128/aac.01316-07
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发表时间：
2008
影响因子：
4.9
通讯作者：
Wagner,RobertD
中科院分区：
文献类型：
--
作者：
Rafii,Fatemeh;Park,Miseon;Bryant,AmyE;Johnson,ShemediaJ;Wagner,RobertD
产气荚膜梭菌诱导的气性坏疽是由强效的细胞外毒素介导的，尤其是α毒素（一种磷脂酶C [PLC]）和θ毒素（一种硫醇激活的细胞溶解素O [PFO]）；而抗生素诱导的毒素合成抑制是一个重要的临床目标。加替沙星诱导的耐氟喹诺酮类c突变株产生PLC和PFO。将携带DNA螺旋酶稳定突变的产气荚膜菌10G与野生型亲本菌株进行了比较。酶谱分析（用羊红细胞和蛋黄覆盖）和时间过程分析（用蛋黄卵磷脂和do -（4硝基苯-磷酰）胆碱水解）表明，菌株10G比WT菌株产生更多的PLC和PFO。菌株10G的毒素产量增加与野生型和突变株之间的生长特性差异无关，也与PLC， PFO或其已知调节蛋白的非同义多态性无关。菌株10G的PLC和PFO产量增加与对HT-29人腺癌细胞的细胞毒活性增加以及血小板-中性粒细胞聚集形成增加有关。另外四种加替沙星诱导的回转酶突变体没有显示出毒素产生的增加，这表明在所有的c菌株中，加替沙星耐药性并不总是与毒素产生的增加有关。perfringens。这是第一份关于氟喹诺酮耐药菌株毒素产量增加的报告。perfringens。
Clostridium perfringens-induced gas gangrene is mediated by potent extracellular toxins, especially alpha toxin (a phospholipase C [PLC]) and theta toxin (perfringolysin O [PFO], a thiol-activated cytolysin); and antibiotic-induced suppression of toxin synthesis is an important clinical goal. The production of PLC and PFO by a gatifloxacin-induced, fluoroquinolone-resistant mutant strain ofC. perfringens, strain 10G, carrying a stable mutation in DNA gyrase was compared with that of the wild-type (WT) parent strain. Zymography (with sheep red blood cell and egg yolk overlays) and time course analysis [with hydrolysis of egg yolk lecithin andO-(4 nitrophenyl-phosphoryl)choline] demonstrated that strain 10G produced more PLC and PFO than the WT strain. Increased toxin production in strain 10G was not related either to differences in growth characteristics between the wild-type and the mutant strain or to nonsynonymous polymorphisms in PLC, PFO, or their known regulatory proteins. Increased PLC and PFO production by strain 10G was associated with increased cytotoxic activity for HT-29 human adenocarcinoma cells and with increased platelet-neutrophil aggregate formation. Four other gatifloxacin-induced gyrase mutants did not show increased toxin production, suggesting that gatifloxacin resistance was not always associated with increased toxin production in all strains ofC. perfringens. This is the first report of increased toxin production in a fluoroquinolone-resistant strain ofC. perfringens.