XerC Contributes to Diverse Forms of Staphylococcus aureus Infection via agr-Dependent and agr-Independent Pathways
XerC Contributes to Diverse Forms of Staphylococcus aureus Infection via agr-Dependent and agr-Independent Pathways
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DOI：
10.1128/iai.01462-15
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发表时间：
2016-04-01
影响因子：
3.1
通讯作者：
Smeltzer, Mark S.
中科院分区：
文献类型：
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作者：
Atwood, Danielle N.;Beenken, Karen E.;Smeltzer, Mark S.
我们证明了xerC的突变限制了耐甲氧西林金黄色葡萄球菌LAC和甲氧西林敏感菌株UAMS-1的生物膜形成。这不是因为这两个菌株细胞内多糖粘附素(PIA)的产生减少，而是因为在UAMS-1xerC突变体中PIA的量增加，而在LAC及其等基因xerC突变体中都检测不到PIA。XerC的突变还导致LAC和UAMS-1的胞外蛋白水解酶和核酸酶的产生增加，限制这两类酶的产生增加了等基因xerC突变体的生物被膜形成。更重要的是，在体内已建立的生物膜的背景下，形成生物膜的能力有限与两个菌株对抗生素敏感性的增加有关。在小鼠菌血症模型中，xerC的突变也降低了毒力，根据内脏的细菌负荷和总体致死率进行了评估。这也导致了α毒素的减少和蛋白A的增加。这些结果表明，xerC可能影响agr的功能状态。通过证明RNAIII和AGRA在LAC和UAMS-1 xerC突变体中的积累减少，证实了这一点。然而，这不能解释xerC突变体的生物膜缺陷表型，因为agr的突变并没有限制这两个菌株的生物膜形成。这些结果表明，xerC对生物膜相关感染和急性菌血症有贡献，这可能分别是由于agr非依赖和依赖的途径。
We demonstrate that mutation of xerC, which reportedly encodes a homologue of an Escherichia coli recombinase, limits biofilm formation in the methicillin-resistant Staphylococcus aureus strain LAC and the methicillin-sensitive strain UAMS-1. This was not due to the decreased production of the polysaccharide intracellular adhesin (PIA) in either strain because the amount of PIA was increased in a UAMS-1 xerC mutant and undetectable in both LAC and its isogenic xerC mutant. Mutation of xerC also resulted in the increased production of extracellular proteases and nucleases in both LAC and UAMS-1, and limiting the production of either class of enzymes increased biofilm formation in the isogenic xerC mutants. More importantly, the limited capacity to form a biofilm was correlated with increased antibiotic susceptibility in both strains in the context of an established biofilm in vivo. Mutation of xerC also attenuated virulence in a murine bacteremia model, as assessed on the basis of the bacterial loads in internal organs and overall lethality. It also resulted in the decreased accumulation of alpha toxin and the increased accumulation of protein A. These findings suggest that xerC may impact the functional status of agr. This was confirmed by demonstrating the reduced accumulation of RNAIII and AgrA in LAC and UAMS-1 xerC mutants. However, this cannot account for the biofilm-deficient phenotype of xerC mutants because mutation of agr did not limit biofilm formation in either strain. These results demonstrate that xerC contributes to biofilm-associated infections and acute bacteremia and that this is likely due to agr-independent and -dependent pathways, respectively.