Subinhibitory concentrations of β-lactam induce haemolytic activity in Staphylococcus aureus through the SaeRS two-component system
Subinhibitory concentrations of β-lactam induce haemolytic activity in Staphylococcus aureus through the SaeRS two-component system
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DOI：
10.1111/j.1574-6968.2006.00568.x
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发表时间：
2007-03-01
影响因子：
2.1
通讯作者：
Hiramatsu, Keiichi
中科院分区：
文献类型：
--
作者：
Kuroda, Hiroko;Kuroda, Makoto;Hiramatsu, Keiichi
SaeRS是一种双组分系统，已被表征为金黄色葡萄球菌中几种毒力因子表达的正调控系统，包括凝固酶、α-、β-和γ-溶血素、核酸酶和纤连蛋白结合蛋白。以前，发现SaeRS系统在转录水平上被β-内酰胺诱导。在这里，我们发现亚抑制浓度的β-内酰胺诱导溶血活性的S。金黄色葡萄球菌N315菌株中，而不是在saeRS无效突变体KSA中。通过微阵列分析比较N315和KSA菌株的转录谱揭示了SaeRS系统调节凝固酶（coa）、α-、β-和γ-溶血素（hla、hlb和hlg）、核酸酶（SA 0746）、纤维蛋白原结合蛋白（emp、ef B、SA 1000和SA 1004）、纤连蛋白结合蛋白B（fnb B）和13种其它基因的调节。此外，使用头孢西丁作为信号诱导剂揭示了SaeRS系统似乎调节22个额外的基因作为次级调节子，包括葡萄球菌辅助调节子SarA和SarT以及Clp蛋白酶ATP酶亚基ClpB和ClpL。这些观察结果表明β-内酰胺能够诱导SaeRS系统，该系统是S.金黄色葡萄球菌的致病性而不是抗菌素耐药性。
SaeRS is a two-component system that has been characterized as a positive regulatory system for the expression of several virulence factors, including coagulase, alpha-, beta- and gamma-haemolysins, nuclease, and fibronectin-binding proteins in Staphylococcus aureus. Previously, the SaeRS system was found to be induced at the transcriptional level by beta-lactam. Here, we found that subinhibitory concentrations of beta-lactam induce haemolytic activity in the S. aureus N315 strain but not in the saeRS null mutant KSA. Comparison of the transcriptional profile of the N315 and KSA strains by microarray analysis reveals that the SaeRS system modulates the regulation of coagulase (coa), alpha-, beta- and gamma-haemolysins (hla, hlb and hlg), nuclease (SA0746), fibrinogen-binding proteins (emp, efb, SA1000 and SA1004), fibronectin-binding protein B (fnbB), and 13 other genes. Further, the use of cefoxitin as a signal inducer reveals that the SaeRS system appears to modulate 22 additional genes as a secondary regulon, including the staphylococcal accessory regulators SarA and SarT and the Clp protease ATPase subunits ClpB and ClpL. These observations suggest that beta-lactam is able to induce the SaeRS system, which acts as a crucial signal transduction system for S. aureus pathogenicity rather than antimicrobial resistance.