Flexible Cobamide Metabolism in Clostridioides (Clostridium) difficile 630 Δerm.
Flexible Cobamide Metabolism in Clostridioides (Clostridium) difficile 630 Δerm.
复制标题
艰难梭菌 (Clostridium) difficile 630 Îerm 中灵活的 Cobamide 代谢。
DOI：
10.1128/jb.00584-19
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发表时间：
2020
影响因子：
3.2
通讯作者：
Taga,MichikoE
中科院分区：
文献类型：
--
作者：
Shelton,AmandaN;Lyu,Xun;Taga,MichikoE
艰难梭菌（Clostridium difficile）是一种机会致病菌，以其在生态失调条件下定殖人类肠道的能力而闻名。它的碳和氨基酸代谢的几个方面已经研究，但它的钴酰胺（维生素B12和相关辅因子）代谢仍然在很大程度上未被探索。C.除了几乎完整的钴酰胺生物合成途径和钴酰胺摄取系统之外，艰难梭菌在其基因组中编码了七条预测的钴酰胺依赖性途径。为了阐明钴酰胺对C. difficile，我们研究了C.艰难梭菌630 Δermand突变体衍生物在钴酰胺依赖性条件下的体外表达。结果表明，C.艰难梭菌可以使用令人惊讶的多种钴酰胺用于甲硫氨酸和脱氧核糖核苷酸合成，并且可以分别使用替代的代谢物或酶来绕过这些钴酰胺依赖性过程。C.艰难梭菌630 Δ erm在提供早期前体5-氨基乙酰丙酸或晚期中间体钴酰胺（Cbi）时产生钴酰胺假钴胺素，并且如果提供替代的低级配体则产生其它钴酰胺。C. difficile 630 Δ erm以微摩尔或更低浓度摄取钴酰胺和Cbi需要转运蛋白BtuFCD。基因组分析表明，不同的C.艰难梭菌菌株，这可能导致吸收钴酰胺和Cbi的能力的差异。这些结果共同表明，像其生理学的其他方面，钴胺代谢在C。机会性病原体艰难梭菌致病的能力与其适应人类肠道微生物群生态失调所产生的条件的倾向密切相关。C的钴胺（维生素B12）代谢。difficile的研究还不充分，尽管它有七个代谢途径，预计需要钴酰胺依赖性酶。在这里，我们表明，C。艰难梭菌的钴酰胺代谢是多功能的，因为它可以使用令人惊讶的多种钴酰胺，并且具有可以绕过其一些钴酰胺需求的替代功能。此外，C.艰难梭菌不能合成钴酰胺，但当给予钴酰胺前体时产生钴酰胺。更好地理解C。艰难梭菌代谢钴酰胺可能导致新的策略，以治疗和预防C。艰难梭相关疾病
Clostridioides(Clostridium)difficileis an opportunistic pathogen known for its ability to colonize the human gut under conditions of dysbiosis. Several aspects of its carbon and amino acid metabolism have been investigated, but its cobamide (vitamin B12and related cofactors) metabolism remains largely unexplored. C. difficile has seven predicted cobamide-dependent pathways encoded in its genome in addition to a nearly complete cobamide biosynthesis pathway and a cobamide uptake system. To address the importance of cobamides to C. difficile, we studied C. difficile 630 Δermand mutant derivatives under cobamide-dependent conditionsin vitro. Our results show that C. difficile can use a surprisingly diverse array of cobamides for methionine and deoxyribonucleotide synthesis and can use alternative metabolites or enzymes, respectively, to bypass these cobamide-dependent processes. C. difficile 630 Δermproduces the cobamide pseudocobalamin when provided the early precursor 5-aminolevulinic acid or the late intermediate cobinamide (Cbi) and produces other cobamides if provided an alternative lower ligand. The ability of C. difficile 630 Δermto take up cobamides and Cbi at micromolar or lower concentrations requires the transporter BtuFCD. Genomic analysis revealed genetic variations in thebtuFCDloci of different C. difficile strains, which may result in differences in the ability to take up cobamides and Cbi. These results together demonstrate that, like other aspects of its physiology, cobamide metabolism in C. difficile is versatile.IMPORTANCEThe ability of the opportunistic pathogen Clostridioides difficile to cause disease is closely linked to its propensity to adapt to conditions created by dysbiosis of the human gut microbiota. The cobamide (vitamin B12) metabolism of C. difficile has been underexplored, although it has seven metabolic pathways that are predicted to require cobamide-dependent enzymes. Here, we show that C. difficile cobamide metabolism is versatile, as it can use a surprisingly wide variety of cobamides and has alternative functions that can bypass some of its cobamide requirements. Furthermore, C. difficile does not synthesize cobamidesde novobut produces them when given cobamide precursors. A better understanding of C. difficile cobamide metabolism may lead to new strategies to treat and prevent C. difficile-associated disease.