Regulation of the intercellular adhesin (ica) locus under anaerobic conditions in Staphylococcus aureus

金黄色葡萄球菌和葡萄球菌的细胞间粘附操纵子产物。表皮细胞合成一个线性的<$1，6连接的葡糖胺聚糖。这种胞外多糖介导细菌粘附和生物膜形成，这被认为是增加与假体生物医学植入物相关的两种病原体的毒力。我们证明了体外厌氧生长导致两种细菌中多糖表达增加。厌氧也显着刺激伊卡-和多糖阳性菌株中ica特异性mRNA的表达。这些数据表明，伊卡基因表达和多糖生产的机制可能作为一个毒力因子在厌氧环境中的体内。这个项目的目的是鉴定和描述在厌氧条件下调控伊卡表达的因子。染色体ICA启动子-β-半乳糖苷酶报告系统将用于在厌氧和需氧条件下伊卡转录的遗传筛选。还将研究两个先前确定的因素（SigB和SsrA/B）对厌氧条件下伊卡活性的影响。最后，当一个S。金黄色葡萄球菌微阵列芯片在本研究过程中变得可用，我们将使用在有氧和厌氧条件下的RNA表达模式来表征调节剂及其靶标。

Products of the intercellular adhesion (ica) operon in Staphylococcus aureus and S. epidermidis synthesize a linear â-1,6 linked glucosaminglycan. This extracellular polysaccharide mediates bacterial adhesion and biofilm formation, which is thought to increase the virulence of both pathogens in association with prosthetic biomedical implants. We demonstrated that anaerobic growth in vitro leads to increased polysaccharide expression in both bacteria. Anaerobiosis also dramatically stimulates ica-specific mRNA expression in ica- and polysaccharide-positive strains. These data suggest a mechanism whereby ica gene expression and polysaccharide production may act as a virulence factor in an anaebobic environment in vivo. This project aims to identify and characterize the factor(s) that regulate ica expression in response to anaerobic conditions. A chromosomal ica-promotor-â-galactosidase reporter system will be used in a genetic screen for ica transcription under anaerobic and aerobic conditions. The influence of two previously identified factors (SigB and SsrA/B) on ica activity under anaerobic conditions will also be investigated. Finally, when a S. aureus micro-array chip becomes available during the course of this study, we will use RNA expression patterns under aerobic and anaerobic conditions to characterize regulator(s) and their target(s).