El Hafi Bassam, Jean-Pierre Fabrice, O'Toole George A
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
bioRxiv. 2024 Oct 21:2024.10.21.619475. doi: 10.1101/2024.10.21.619475.
Cystic fibrosis (CF) is a multi-organ genetic disorder that affects more than 100,000 individuals worldwide. Chronic respiratory infections are among the hallmark complications associated with CF lung disease, and these infections are often due to polymicrobial communities that colonize the airways of persons with CF (pwCF). Such infections are a significant cause of morbidity and mortality, with studies indicating that pwCF who are co-infected with more than one organism experience more frequent pulmonary exacerbations, leading to a faster decline in lung function. Previous work established an CF-relevant polymicrobial community model composed of , , , and . cannot survive in monoculture in this model. In this study, we leverage this model to investigate the interactions between and , allowing us to understand the mechanisms by which the two microbes interact to support the growth of specifically in the context of the polymicrobial community. We demonstrate a cross-feeding mechanism whereby metabolizes mucin into short-chain fatty acids that are in turn utilized by and converted into metabolites (succinate, acetate) that are cross-fed to , supporting the survival of this anaerobe in the CF lung-relevant model.
囊性纤维化（CF）是一种多器官遗传性疾病，全球有超过10万人受其影响。慢性呼吸道感染是与CF肺部疾病相关的标志性并发症之一，这些感染通常是由定植于CF患者（pwCF）气道的多种微生物群落引起的。此类感染是发病和死亡的重要原因，研究表明，同时感染多种病原体的pwCF会更频繁地出现肺部病情加重，导致肺功能更快下降。先前的研究建立了一个与CF相关的多种微生物群落模型，该模型由[具体微生物1]、[具体微生物2]、[具体微生物3]和[具体微生物4]组成。在这个模型中，[具体微生物4]无法在单一培养中存活。在本研究中，我们利用这个模型来研究[具体微生物1]和[具体微生物2]之间的相互作用，从而使我们能够了解这两种微生物在多种微生物群落背景下相互作用以支持[具体微生物1]生长的机制。我们展示了一种交叉喂养机制，即[具体微生物2]将粘蛋白代谢为短链脂肪酸，这些短链脂肪酸进而被[具体微生物1]利用并转化为代谢产物（琥珀酸盐、乙酸盐），这些代谢产物又被交叉供给[具体微生物3]，从而支持这种厌氧菌在与CF肺部相关的模型中的存活。
