A cortex-specific PBP contributes to cephalosporin resistance in Clostridium difficile

A cortex-specific PBP contributes to cephalosporin resistance in Clostridium difficile
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皮质特异性 PBP 导致艰难梭菌对头孢菌素耐药

DOI:
10.1101/715458
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发表时间:
2019
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Alabdali Y
Alabdali Y
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作者:
Alabdali Y

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孢子形成是一个复杂的细胞分化程序,由许多厚壁菌门成员共享,其最终结果是一个高度抗性的,代谢惰性的孢子,可以在恶劣的环境中生存。艰难梭状芽孢杆菌是疾病传播所必需的,也是反复感染所必需的。然而,尽管与研究得很好的枯草芽孢杆菌系统有相似之处,但对孢子形成的分子基础知之甚少。孢子包膜由多层保护层组成,其中一层是肽聚糖的特殊层,称为皮层,它对孢子的抗性特性至关重要。我们已经确定并表征了一种青霉素结合蛋白(PBP),这是皮层合成艰难梭菌所必需的。令人惊讶的是,这种PBP也被发现有助于头孢菌素耐药性,表明在营养细胞壁的合成中有额外的作用。这是第一次描述皮层特异性PBP困难,并开始揭示这种重要病原体的皮层生物发生过程。
Sporulation is a complex cell differentiation programme shared by many members of the Firmicutes, the end result of which is a highly resistant, metabolically inert spore that can survive harsh environmental insults.Clostridium difficilespores are essential for transmission of disease and are also required for recurrent infection. However, the molecular basis of sporulation is poorly understood, despite parallels with the well-studiedBacillus subtilissystem. The spore envelope consists of multiple protective layers, one which is a specialised layer of peptidoglycan, called the cortex, that is essential for the resistant properties of the spore. We have identified and characterised a penicillin binding protein (PBP) that is required for cortex synthesis inC. difficile. Surprisingly this PBP was also found to contribute to cephalosporin resistance, indicating an additional role in the synthesis of vegetative cell wall. This is the first description of a cortex-specific PBP inC. difficileand begins the process of unravelling cortex biogenesis in this important pathogen.
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