Transcriptional Regulation of icaADBC by both IcaR and TcaR in Staphylococcus epidermidis
Transcriptional Regulation of icaADBC by both IcaR and TcaR in Staphylococcus epidermidis
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DOI：
10.1128/jb.00524-18
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发表时间：
2019-03-01
影响因子：
3.2
通讯作者：
Fey, P. D.
中科院分区：
文献类型：
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作者：
Hoang, Tra-My;Zhou, C.;Fey, P. D.
表皮葡萄球菌是人类生物膜介导感染的主要原因，原因是附着在异物上。葡萄球菌生物膜积累的主要分子是多糖胞内粘附素（PIA），它是由icaADBC操纵子编码的酶合成的。PIA的表达在临床分离株中变化很大，这表明PIA的表达水平在宿主的某些生态位中是有选择的。然而，控制这些分离株中icaADBC转录和PIA合成增强的机制尚不清楚。我们假设这些分离株中PIA合成的增强是由于IcaR和/或TcaR的功能。因此，我们对两个具有不同icaADBC转录和PIA表达水平的表皮葡萄球菌分离株（1457和CSF41498）进行了研究。在1457和CSF41498中，icaR和tcaR的组成表达表明这两种抑制因子都是功能性的，可以完全抑制icaADBC的转录。然而，我们发现IcaR是CSF41498的主要抑制因子，TcaR是1457的主要抑制因子。进一步分析表明，与CSF41498相比，icaR转录在1457中受到抑制，这表明TcaR仅在icaR缺失的情况下发挥抑制作用。事实上，DNase I足迹表明IcaR和TcaR可能结合在IcaR - icaa基因间区域的同一位点上。最后，我们发现从1457和CSF41498中可以快速选择表达不同数量PIA的突变体。总的来说，我们提出，通过几种抑制icaR转录的遗传机制，在宿主的某些生态位中选择产生增强PIA合成的菌株，从而增加PIA合成。表皮葡萄球菌是一种寄生在我们皮肤上的共生细菌。作为一种共生体，它通过多种机制保护人类免受细菌病原体的侵害。然而，由于它与塑料的结合能力，它也是生物膜感染的一个重要原因。多糖细胞间黏附素是生物膜的重要组成部分，我们认为这种多糖的表达在某些宿主壁龛中是有益的，例如当细菌在导管腔内定植时提供额外的强度，而在其他壁龛中则是有害的，例如在皮肤表面定植。我们在这里表明，icaADBC转录的微调，从而PIA合成，是通过两个转录抑制因子，IcaR和TcaR介导的。
S. epidermidis is a primary cause of biofilm-mediated infections in humans due to adherence to foreign bodies. A major staphylococcal biofilm accumulation molecule is polysaccharide intracellular adhesin (PIA), which is synthesized by enzymes encoded by the icaADBC operon. Expression of PIA is highly variable among clinical isolates, suggesting that PIA expression levels are selected in certain niches of the host. However, the mechanisms that govern enhanced icaADBC transcription and PIA synthesis in these isolates are not known. We hypothesized that enhanced PIA synthesis in these isolates was due to function of IcaR and/or TcaR. Thus, two S. epidermidis isolates (1457 and CSF41498) with different icaADBC transcription and PIA expression levels were studied. Constitutive expression of both icaR and tcaR demonstrated that both repressors are functional and can completely repress icaADBC transcription in both 1457 and CSF41498. However, it was found that IcaR was the primary repressor for CSF41498 and TcaR was the primary repressor for 1457. Further analysis demonstrated that icaR transcription was repressed in 1457 in comparison to CSF41498, suggesting that TcaR functions as a repressor only in the absence of IcaR. Indeed, DNase I footprinting suggests IcaR and TcaR may bind to the same site within the icaR-icaA intergenic region. Lastly, we found mutants expressing variable amounts of PIA could rapidly be selected from both 1457 and CSF41498. Collectively, we propose that strains producing enhanced PIA synthesis are selected within certain niches of the host through several genetic mechanisms that function to repress icaR transcription, thus increasing PIA synthesis.IMPORTANCE Staphylococcus epidermidis is a commensal bacterium that resides on our skin. As a commensal, it protects humans from bacterial pathogens through a variety of mechanisms. However, it is also a significant cause of biofilm infections due to its ability to bind to plastic. Polysaccharide intercellular adhesin is a significant component of biofilm, and we propose that the expression of this polysaccharide is beneficial in certain host niches, such as providing extra strength when the bacterium is colonizing the lumen of a catheter, and detrimental in others, such as colonization of the skin surface. We show here that fine-tuning of icaADBC transcription, and thus PIA synthesis, is mediated via two transcriptional repressors, IcaR and TcaR.