Essential Role for the Major Autolysin in the Fibronectin-Binding Protein-Mediated Staphylococcus aureus Biofilm Phenotype
Essential Role for the Major Autolysin in the Fibronectin-Binding Protein-Mediated Staphylococcus aureus Biofilm Phenotype
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DOI：
10.1128/iai.00364-10
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发表时间：
2011-03-01
影响因子：
3.1
通讯作者：
O'Gara, James P.
中科院分区：
文献类型：
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作者：
Houston, Patrick;Rowe, Sarah E.;O'Gara, James P.
金黄色葡萄球菌临床分离株能够产生至少两种不同类型的由纤连蛋白结合蛋白（FnBP）或icaADBC编码的多糖细胞间粘附素（PIA）介导的生物膜。在12株临床耐甲氧西林链球菌中，主要自溶素基因atl的缺失降低了初级附着率，并损害了亲水性聚苯乙烯上FnBP依赖性生物膜的产生。金黄色葡萄球菌（MRSA）分离株，但对9个甲氧西林敏感的S.金黄色葡萄球菌（MSSA）分离株。相反，Atl是疏水聚苯乙烯上FnBP和PIA介导的生物膜发育所需的。在这里，我们研究了Atl在亲水性聚苯乙烯上的生物膜生产中的作用。抑制RNAIII表达和细胞外蛋白酶产生的另一种σ因子σ（B）是FnBP依赖性生物膜而非PIA依赖性生物膜发育所需的。此外，agr位点的突变增强了FnBP依赖的生物膜的发展，而sarA突变，增加蛋白酶的产生，阻断FnBP介导的生物膜的发展。在MRSA分离株BH 1CC中sigB的突变降低了初级附着率，部分是通过降低atl转录。翻译后激活或抑制Atl活性与苯甲基磺酰氟和聚茴香脑磺酸钠或突变的Atl酰胺酶活性位点干扰裂解活性和生物膜的发展。与这些观察结果一致，细胞外DNA对于Atl/FnBP依赖性生物膜发育的早期阶段是重要的。对atl调控的进一步分析显示atlR编码主要自溶素的转录抑制因子，并且BH 1CC中的atlR：：Tc-r突变增强了生物膜形成能力。这些数据揭示了主要自溶素在FnBP依赖性S.金黄色葡萄球菌生物膜表型。
Staphylococcus aureus clinical isolates are capable of producing at least two distinct types of biofilm mediated by the fibronectin-binding proteins (FnBPs) or the icaADBC-encoded polysaccharide intercellular adhesin (PIA). Deletion of the major autolysin gene atl reduced primary attachment rates and impaired FnBP-dependent biofilm production on hydrophilic polystyrene in 12 clinical methicillin-resistant S. aureus (MRSA) isolates but had no effect on PIA-dependent biofilm production by 9 methicillin-susceptible S. aureus (MSSA) isolates. In contrast, Atl was required for both FnBP- and PIA-mediated biofilm development on hydrophobic polystyrene. Here we investigated the role of Atl in biofilm production on hydrophilic polystyrene. The alternative sigma factor sigma(B), which represses RNAIII expression and extracellular protease production, was required for FnBP-but not PIA-dependent biofilm development. Furthermore, mutation of the agr locus enhanced FnBP-dependent biofilm development, whereas a sarA mutation, which increases protease production, blocked FnBP-mediated biofilm development. Mutation of sigB in MRSA isolate BH1CC lowered primary attachment rates, in part via reduced atl transcription. Posttranslational activation or inhibition of Atl activity with phenylmethylsulfonyl fluoride and polyanethole sodium sulfonate or mutation of the Atl amidase active site interfered with lytic activity and biofilm development. Consistent with these observations, extracellular DNA was important for the early stages of Atl/FnBP-dependent biofilm development. Further analysis of atl regulation revealed that atlR encodes a transcriptional repressor of the major autolysin and that an atlR:: Tc-r mutation in BH1CC enhanced biofilm-forming capacity. These data reveal an essential role for the major autolysin in the early events of the FnBP-dependent S. aureus biofilm phenotype.