Regulation of para-cresol production in Clostridioides difficile
Regulation of para-cresol production in Clostridioides difficile
复制标题
艰难梭菌中对甲酚生产的调节
DOI：
10.1016/j.mib.2021.11.005
复制
发表时间：
2022
影响因子：
5.4
通讯作者：
Harrison M
中科院分区：
文献类型：
--
作者：
Harrison M
高光甲酚选择性地抑制肠道微生物中某些分类群的生长。对甲酚的生产为艰难梭菌提供了在活体中的竞争优势。对甲酚可以通过酪氨酸发酵或使用外源p-HPA来生产。升高的对甲酚可以诱导对甲酚的产生。由hpdBCA操纵子编码的HpdBCA脱羧酶将对-HPA转化为对-甲酚。人类病原体艰难梭菌在抗生素暴露后定居在胃肠道，这会对有益的微生物群造成干扰。艰难梭菌在肠道微生物群中的一个不同寻常的特征是它能够产生高浓度的抗菌化合物对甲酚，这种化合物选择性地针对革兰氏阴性细菌。对甲酚的产生有两种方式：(A)通过中间体对羟基苯乙酸酯(p-HPA)进行酪氨酸发酵，或(B)外源p-HPA在人体肠道内直接周转。在hpdBCA操纵子编码的HpdBCA脱羧酶的作用下，p-HPA脱羧基生成对甲酚。HpdBCA脱羧酶的产生是由p-HPA的升高在转录水平上诱导的，这会导致对甲酚的产生增加，从而显著降低微生物组的多样性和丰富度。对甲酚对肠道有益微生物群的这种有害作用有利于艰难梭菌的致病和感染复发。抑制这一途径将提供高度特异的治疗方法。
Highlightsp-cresol selectively inhibits growth of certain taxa in the gut microbiome.p-cresol production provides C. difficile with a competitive advantage in vivo.p-cresol can be produced from fermentation of tyrosine or using exogenous p-HPA.Elevated p-HPA induces production of p-cresol.HpdBCA decarboxylase, encoded by hpdBCA operon converts p-HPA to p-cresol.The human pathogen Clostridioides difficile colonises the gastrointestinal tract following antibiotic exposure, which causes perturbations in the beneficial microbiome. An unusual feature of C. difficile among the gut microbiota is its ability to produce high concentrations of the antimicrobial compound para-cresol, which selectively targets Gram-negative bacteria. Production of p-cresol occurs either by:(a) tyrosine fermentation via the intermediate para-hydroxyphenylacetate (p-HPA), or (b) direct turnover of exogenous p-HPA in the human gut. p-HPA is decarboxylated to produce p-cresol, by the action of HpdBCA decarboxylase encoded by the hpdBCA operon. HpdBCA decarboxylase production is induced at the transcriptional level by elevated p-HPA, which causes elevated p-cresol production, that significantly reduces microbiome diversity and richness. This deleterious effect of p-cresol on the beneficial gut microbiome is advantageous for C. difficile pathogenesis and infection relapse. Inhibiting this pathway would provide a highly specific therapeutic.