Pathogenesis of Staphylococcus aureus is attributed to its remarkable adaptation to changes in the environment, mediated by the arsenal of virulence factors, which are regulated by intricate mechanisms that include small RNAs (sRNAs) as important regulatory molecules. The sRNA SprX was previously described to be involved in the regulation of S. aureus pathogenicity, by modifying the expression of surface-associated clumping factor B and the secreted delta haemolysin. This study describes the regulation by SprX, of expression of multiple autolysins, which play an essential role in cell wall metabolism and function as important virulence factors that facilitate adhesion, internalization, and immune evasion during S. aureus colonization and pathogenesis. SprX acts by positively regulating the expression of autolysin regulator WalR. Overexpression of SprX resulted in differential regulation of autolysins IsaA, and LytM, while WalR levels were unchanged. SprX knockdown strain exhibited down-regulation of multiple autolytic bands corresponding to the major autolysin AtlA and its process intermediates in cell wall degradation zymography, and 0.2 to 0.1 fold reduction of lytM, atlA, isaA, and walR transcripts in qRT-PCRs. Down-regulation of SprX resulted in altered phenotype with high cell aggregation as analyzed by SEM, decrease in biofilm formation and higher resistance to Triton X-100-induced lysis, all of which indicate that SprX is essential for expression of autolysins. A putative RNA-RNA interaction was indicated in silico between SprX and walR mRNA and further confirmed by in vitro RNA-RNA interaction in electrophoretic mobility shift assays. These findings elucidate a new mechanism in which SprX modulates the S. aureus pathogenicity by regulating the regulator of autolysins in cell wall metabolism and as virulence factors.

金黄色葡萄球菌的发病机制归因于其对环境变化的显着适应，由毒力因子库介导，毒力因子由复杂的机制调节，其中包括作为重要调节分子的小 RNA (sRNA)。sRNA SprX 先前被描述为参与调节金黄色葡萄球菌的致病性，通过修改表面相关的聚集因子 B 和分泌的 delta 溶血素的表达。本研究描述了 SprX 对多种自溶素表达的调节，这些自溶素在细胞壁代谢中起重要作用，并作为重要的毒力因子在金黄色葡萄球菌期间促进粘附、内化和免疫逃避定植和发病机制。SprX 通过积极调节自溶素调节剂 WalR 的表达发挥作用。SprX 的过度表达导致自溶素 IsaA 和 LytM 的差异调节，而 WalR 水平没有变化。对应于所述主要自溶素和ATLA在细胞壁降解酶谱其方法中的中间体的多个自溶频带SPRX敲低应变表现出下调，和0.2至0.1倍的减少的lytM，ATLA，ISAA和walRqRT-PCR 中的转录本。根据 SEM 分析，SprX 的下调导致表型改变，细胞聚集程度高，生物膜形成减少，对 Triton X-100 诱导的裂解具有更高的抵抗力，所有这些都表明 SprX 对自溶素的表达至关重要。推定的 RNA-RNA 相互作用在 SprX 和walR mRNA之间用计算机模拟显示，并通过电泳迁移率变化测定中的体外RNA-RNA 相互作用进一步证实。这些发现阐明了一种新机制，其中 SprX通过调节细胞壁代谢中自溶素的调节剂和作为毒力因子来调节金黄色葡萄球菌的致病性。