Impact of the phi027 bacteriophage on virulence and physiology of lysogenic Clostridioides difficile

<p><em style="border-style:solid;border-width:0px;font-family:&#39;pplxserif&#39; , &#39;pplxserif&#39; , &#39;ui-serif&#39; , &#39;georgia&#39; , &#39;cambria&#39; , &#39;hiragino mincho pron&#39; , &#39;yu mincho&#39; , &#39;songti sc&#39; , &#39;simsun&#39; , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;songti tc&#39; , , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;applemyungjo&#39; , &#39;batang&#39; , serif;font-size:16px">Clostridioides difficile</em><span style="font-family:&#39;pplxserif&#39; , &#39;pplxserif&#39; , &#39;ui-serif&#39; , &#39;georgia&#39; , &#39;cambria&#39; , &#39;hiragino mincho pron&#39; , &#39;yu mincho&#39; , &#39;songti sc&#39; , &#39;simsun&#39; , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;songti tc&#39; , , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;applemyungjo&#39; , &#39;batang&#39; , serif;font-size:16px">, the causative agent of CDI, can be infected by temperate bacteriophages integrating into the host genome. Such lysogeny may affect bacterial physiology and virulence. The phiCDKH02 bacteriophage, identified in clinical </span><em style="border-style:solid;border-width:0px;font-family:&#39;pplxserif&#39; , &#39;pplxserif&#39; , &#39;ui-serif&#39; , &#39;georgia&#39; , &#39;cambria&#39; , &#39;hiragino mincho pron&#39; , &#39;yu mincho&#39; , &#39;songti sc&#39; , &#39;simsun&#39; , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;songti tc&#39; , , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;applemyungjo&#39; , &#39;batang&#39; , serif;font-size:16px">C. difficile</em><span style="font-family:&#39;pplxserif&#39; , &#39;pplxserif&#39; , &#39;ui-serif&#39; , &#39;georgia&#39; , &#39;cambria&#39; , &#39;hiragino mincho pron&#39; , &#39;yu mincho&#39; , &#39;songti sc&#39; , &#39;simsun&#39; , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;songti tc&#39; , , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;applemyungjo&#39; , &#39;batang&#39; , serif;font-size:16px"> isolates of ribotypes 027 and 176, was found to be identical to phage phi027. Using CRISPR-Cpf1 technology, the prophage was removed from the lysogenic strain to assess its impact. The cured strain showed altered sporulation, reduced adhesion, and lower cytopathic effects on colon cells due to decreased TcdB production. These results indicate that prophages play an important role in modulating </span><em style="border-style:solid;border-width:0px;font-family:&#39;pplxserif&#39; , &#39;pplxserif&#39; , &#39;ui-serif&#39; , &#39;georgia&#39; , &#39;cambria&#39; , &#39;hiragino mincho pron&#39; , &#39;yu mincho&#39; , &#39;songti sc&#39; , &#39;simsun&#39; , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;songti tc&#39; , , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;applemyungjo&#39; , &#39;batang&#39; , serif;font-size:16px">C. difficile</em><span style="font-family:&#39;pplxserif&#39; , &#39;pplxserif&#39; , &#39;ui-serif&#39; , &#39;georgia&#39; , &#39;cambria&#39; , &#39;hiragino mincho pron&#39; , &#39;yu mincho&#39; , &#39;songti sc&#39; , &#39;simsun&#39; , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;songti tc&#39; , , &#39;songti tc&#39; , &#39;pmingliu&#39; , &#39;applemyungjo&#39; , &#39;batang&#39; , serif;font-size:16px"> virulence.</span></p>

艰难梭菌（Clostridioides difficile）作为艰难梭菌感染（CDI）的致病菌，可被整合至宿主基因组的温和噬菌体侵染。此类溶原性状态可影响细菌的生理特性与致病力。研究人员从核糖体分型为027和176的临床分离艰难梭菌（C. difficile）菌株中鉴定出phiCDKH02噬菌体，经确认其与phi027噬菌体完全一致。本研究利用CRISPR-Cpf1技术，将该前噬菌体从溶原菌株中移除以评估其作用。经清除前噬菌体的菌株表现出芽孢形成能力改变、黏附能力下降，且由于TcdB（艰难梭菌毒素B）表达量降低，其对结肠细胞的细胞病变效应也有所减弱。上述结果表明，前噬菌体在调控艰难梭菌的致病力方面发挥着重要作用。