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与生态失调相关的肠道细菌在利用关键粘蛋白成分唾液酸的能力上存在菌株水平的差异。

Dysbiosis-associated gut bacterium varies at the strain level in its ability to utilize key mucin component sialic acid.

作者信息

Sokolovskaya Olga M, Uzunovic Jasmina, Peng Yutian, Okumura Mikiko, Wang Lingjue Mike, Zhou Yuhui, Lai Zijuan, Skippington Elizabeth, Tan Man-Wah

机构信息

Department of Infectious Diseases & Host-Microbe Interactions, Genentech, Inc., South San Francisco, California, USA.

Department of OMNI Bioinformatics, Genentech Inc., South San Francisco, California, USA.

出版信息

Microbiol Spectr. 2025 Jul 11:e0309024. doi: 10.1128/spectrum.03090-24.

Abstract

UNLABELLED

is a prevalent human gut commensal bacterium with known roles in intestinal mucus degradation, including by catabolism of the terminal mucin sugar sialic acid. While is not considered a pathogen, overabundance of this species is correlated with inflammatory bowel disease (IBD), and its sialic acid metabolism may play a role in the dysbiotic state. Interestingly, liberation of mucin-bound sialic acid by yields the distinct product of 2,7-anhydro-N-acetylneuraminic acid (2,7-anhydro-Neu5Ac), in contrast to other known mucin-degrading bacteria, which generate Neu5Ac. This prompted us to look for 2,7-anhydro-Neu5Ac metabolism proteins in the genomes of 77 clinical isolates. We found that 2,7-anhydro-Neu5Ac metabolism is sporadically distributed in this species with respect to phylogeny and strain origin. We measured sialic acid-dependent growth of 12 sequenced isolates, finding that the presence of 2,7-anhydro-Neu5Ac catabolism proteins was predictive of growth on this substrate. Our analysis also uncovered "partial" 2,7-anhydro-Neu5Ac catabolism pathways in two strains, leading to the discovery that these strains grow with Neu5Ac as a sole carbon source, a metabolic capability previously unreported in this species. These results reveal a notable diversity of sialic acid catabolism across the species, an essential consideration for further investigations into the importance of this metabolism in mucin degradation and in the roles of in IBD and other gut dysbioses.

IMPORTANCE

is a common resident of the human gut, but often blooms in inflammatory bowel disease (IBD). It remains unclear whether plays any direct role in disease occurrence. This study investigates utilization of sialic acid, a crucial component of host mucins, the main constituents of the mucus that lines and protects the gut. We profile variations in sialic acid metabolic pathways and growth among 77 strains, isolated from healthy people and individuals with IBD, discovering further diversity in sialic acid utilization than was previously appreciated. This study emphasizes that the intricate interaction between bacteria and their environment must be examined at the strain level to understand the roles of particular species in health and disease.

摘要

未标记

是一种常见的人体肠道共生细菌,在肠道黏液降解中发挥着已知作用,包括通过分解末端黏蛋白糖唾液酸来实现。虽然不被视为病原体,但该物种数量过多与炎症性肠病(IBD)相关,其唾液酸代谢可能在生态失调状态中起作用。有趣的是,与其他已知的黏蛋白降解细菌产生N - 乙酰神经氨酸(Neu5Ac)不同,通过分解黏蛋白结合的唾液酸会产生独特的产物2,7 - 脱水 - N - 乙酰神经氨酸(2,7 - 脱水 - Neu5Ac)。这促使我们在77株临床分离株的基因组中寻找2,7 - 脱水 - Neu5Ac代谢蛋白。我们发现,就系统发育和菌株来源而言,2,7 - 脱水 - Neu5Ac代谢在该物种中呈散在分布。我们测量了12株测序分离株依赖唾液酸的生长情况,发现存在2,7 - 脱水 - Neu5Ac分解代谢蛋白可预测在该底物上的生长。我们的分析还在两株菌株中发现了“部分”2,7 - 脱水 - Neu5Ac分解代谢途径,从而发现这些菌株能够以Neu5Ac作为唯一碳源生长,这是该物种此前未报道过的一种代谢能力。这些结果揭示了该物种在唾液酸分解代谢方面存在显著多样性,这对于进一步研究这种代谢在黏蛋白降解以及在IBD和其他肠道生态失调中的作用的重要性而言是一个重要的考虑因素。

重要性

是人体肠道的常见寄居菌,但在炎症性肠病(IBD)中常大量繁殖。目前尚不清楚它在疾病发生中是否起任何直接作用。本研究调查了对唾液酸的利用情况,唾液酸是宿主黏蛋白的关键成分,而黏蛋白是肠道内衬和保护肠道的黏液的主要成分。我们分析了从健康人和IBD患者中分离出的77株菌株在唾液酸代谢途径和生长方面的差异,发现唾液酸利用的多样性比之前认识到的更多。这项研究强调必须在菌株水平上研究细菌与其环境之间复杂的相互作用,以了解特定物种在健康和疾病中的作用。

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