Proteolytic activity of surface-exposed HtrA determines its expression level and is needed to survive acidic conditions in Clostridioides difficile,Molecular Microbiology

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Proteolytic activity of surface-exposed HtrA determines its expression level and is needed to survive acidic conditions in Clostridioides difficile
Molecular Microbiology ( IF 2.6 ) Pub Date : 2024-07-30 , DOI: 10.1111/mmi.15300
Jeroen Corver ₁ , Bart Claushuis ₁ , Tatiana M Shamorkina _{1,

2} , Arnoud H de Ru ₂ , Merle M van Leeuwen ₁ , Paul J Hensbergen ₂ , Wiep Klaas Smits ₁

Affiliation

To survive in the host, pathogenic bacteria need to be able to react to the unfavorable conditions that they encounter, like low pH, elevated temperatures, antimicrobial peptides and many more. These conditions may lead to unfolding of envelope proteins and this may be lethal. One of the mechanisms through which bacteria are able to survive these conditions is through the protease/foldase activity of the high temperature requirement A (HtrA) protein. The gut pathogen Clostridioides difficile encodes one HtrA homolog that is predicted to contain a membrane anchor and a single PDZ domain. The function of HtrA in C. difficile is hitherto unknown but previous work has shown that an insertional mutant of htrA displayed elevated toxin levels, less sporulation and decreased binding to target cells. Here, we show that HtrA is membrane associated and localized on the surface of C. difficile and characterize the requirements for proteolytic activity of recombinant soluble HtrA. In addition, we show that the level of HtrA in the bacteria heavily depends on its proteolytic activity. Finally, we show that proteolytic activity of HtrA is required for survival under acidic conditions.

中文翻译：

表面暴露的 HtrA 的蛋白水解活性决定了其表达水平，并且在艰难梭菌的酸性条件下生存是必要的

为了在宿主中生存，病原菌需要能够对它们遇到的不利条件做出反应，例如低 pH 值、高温、抗菌肽等等。这些情况可能导致包膜蛋白展开，这可能是致命的。细菌能够在这些条件下生存的机制之一是通过高温需求 A （HtrA）蛋白的蛋白酶/折叠酶活性。肠道病原体艰难梭菌编码一个 HtrA 同源物，预计该同源物包含一个膜锚和一个 PDZ 结构域。HtrA 在艰难梭菌中的功能迄今为止尚不清楚，但以前的研究表明，htrA 的插入突变体表现出毒素水平升高、孢子形成减少和与靶细胞结合降低。在这里，我们表明 HtrA 是膜相关并位于艰难梭菌表面的，并表征了重组可溶性 HtrA 的蛋白水解活性的要求。此外，我们表明细菌中 HtrA 的水平在很大程度上取决于其蛋白水解活性。最后，我们表明 HtrA 的蛋白水解活性是在酸性条件下存活所必需的。

更新日期：2024-07-30

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