DIMINISHED VIRULENCE OF A SAR(-)/AGR(-) MUTANT OF STAPHYLOCOCCUS-AUREUS IN THE RABBIT MODEL OF ENDOCARDITIS
DIMINISHED VIRULENCE OF A SAR(-)/AGR(-) MUTANT OF STAPHYLOCOCCUS-AUREUS IN THE RABBIT MODEL OF ENDOCARDITIS
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DOI：
10.1172/jci117530
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发表时间：
1994-11-01
影响因子：
15.9
通讯作者：
BAYER, AS
中科院分区：
文献类型：
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作者：
CHEUNG, AL;EBERHARDT, KJ;BAYER, AS
金黄色葡萄球菌的微生物致病性是一个复杂的过程，涉及许多毒力基因，这些毒力基因受到 sar 和 agr 等全球调控系统的调控。为了评估这两个位点在毒力中的作用，我们构建了菌株 RN6390 和 RN450 的 sar(-)lagr(-) 突变体，并将它们的表型特征与相应的单个 sar(-) 和 agr(-) 突变体和亲本进行了比较。 sar(-)lagr(-) 突变体中不存在所有溶血素的分泌，而单个agr(-) 突变体中仍保留残留的β-溶血素活性。与亲本相比，单sar(-)突变体和双突变体中的纤连蛋白结合能力均显着降低，而双突变体中纤维蛋白原结合能力的降低是适度的。在兔心内膜炎模型中，尽管各个攻击组的早期菌血症水平相当，但在接种 10(3)-10(6) CFU 时，与亲本 (RN6390) 相比，双突变体的感染率和植内细菌密度均显着降低。值得注意的是，在攻击后 30 分钟（10(6) CFU），双突变组中粘附在瓣膜赘生物上的细菌少于亲本组。这些研究表明，sar 和 agr 基因座均与心内膜炎中金黄色葡萄球菌的初始瓣膜粘附、植被内持久性和增殖有关。
Microbial pathogenicity in Staphylococcus aureus is a complex process involving a number of virulence genes that are regulated by global regulatory systems including sar and agr. To evaluate the roles of these two loci in virulence, we constructed sar(-)lagr(-) mutants of strains RN6390 and RN450 and compared their phenotypic profiles to the corresponding single sar(-) and agr(-) mutants and parents. The secretion of all hemolysins was absent in the sar(-)lagr(-) mutants while residual beta-hemolysin activity remained in single agr(-) mutants. The fibronectin binding capacity was significantly diminished in both single sar(-) mutants and double mutants when compared with parents while the reduction in fibrinogen binding capacity in the double mutants was modest. In the rabbit endocarditis model, there was a significant decrease in both infectivity rates and intravegetation bacterial densities with the double mutant as compared to the parent (RN6390) at 10(3)-10(6) CFU inocula despite comparable levels of early bacteremia among various challenge groups. Notably, fewer bacteria in the double mutant group adhered to valvular vegetations at 30 min after challenge (10(6) CFU) than the parent group. These studies suggest that both the sar and agr loci are involved in initial valvular adherence, intravegetation persistence and multiplication of S. aureus in endocarditis.