陰道乳酸桿菌脂肪酸反應機制揭示針對代謝物的細菌性陰道病治療策略

作者：小柯機器人 發布時間：2024/8/21 16:10:31

本期文章：《細胞—代謝》：Online/在線發表

美國哈佛醫學院Douglas S. Kwon等研究人員合作發現，陰道乳酸桿菌脂肪酸反應機制揭示針對代謝物的細菌性陰道病治療策略。2024年8月19日，國際知名學術期刊《細胞》在線發表了這一成果。

研究人員表示，細菌性陰道病（BV），一種以乳酸桿菌缺乏為特征的常見綜合癥，與不良健康結果相關。BV在標準抗生素治療后經常復發，部分原因是抗生素促進了Lactobacillus iners的微生物群主導地位，而不是Lactobacillus crispatus，這種菌株具有更有利的健康關聯。因此，需要促進L. crispatus和抑制L. iners的策略。

研究人員發現，油酸（OA）和類似的長鏈脂肪酸能夠同時抑制L. iners和增強L. crispatus的生長。這些表型需要OA誘導的基因，這些基因在L. crispatus和相關的乳酸桿菌中保守，包括油酸水合酶（ohyA）和推測的脂肪酸外排泵（farE）。FarE介導了對OA的抗性，而OhyA在陰道微生物群中活性強，通過生化方式將OA隔離為僅ohyA攜帶的生物體可以利用的衍生形式，從而提高了細菌的適應性。OA在體外BV模型中比抗生素更有效地促進了L. crispatus的主導地位，表明代謝物基礎的治療方法可能是一種有效的干預策略。

附：英文原文

Title: Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment

Author: Meilin Zhu, Matthew W. Frank, Christopher D. Radka, Sarah Jeanfavre, Jiawu Xu, Megan W. Tse, Julian Avila Pacheco, Jae Sun Kim, Kerry Pierce, Amy Deik, Fatima Aysha Hussain, Joseph Elsherbini, Salina Hussain, Nondumiso Xulu, Nasreen Khan, Vanessa Pillay, Caroline M. Mitchell, Krista L. Dong, Thumbi Ndungu, Clary B. Clish, Charles O. Rock, Paul C. Blainey, Seth M. Bloom, Douglas S. Kwon

Issue&Volume: 2024-08-19

Abstract: Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.

DOI: 10.1016/j.cell.2024.07.029

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00823-7

期刊信息

Cell Metabolism：《細胞—代謝》，創刊于2005年。隸屬于細胞出版社，最新IF：31.373

官方網址：https://www.cell.com/cell-metabolism/home

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