Pseudomonas aeruginosasupports the survival ofPrevotella melaninogenicain a cystic fibrosis lung polymicrobial community through metabolic cross-feeding

Abstract

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 anin vitroCF-relevant polymicrobial community model composed ofP. aeruginosa,S. aureus,S. sanguinis, andP. melaninogenica.P. melaninogenicacannot survive in monoculture in this model. In this study, we leverage this model to investigate the interactions betweenP. aeruginosaandP. melaninogenica, allowing us to understand the mechanisms by which the two microbes interact to support the growth ofP. melaninogenicaspecifically in the context of the polymicrobial community. We demonstrate a cross-feeding mechanism wherebyP. melaninogenicametabolizes mucin into short-chain fatty acids that are in turn utilized byP. aeruginosaand converted into metabolites (succinate, acetate) that are cross-fed toP. melaninogenica, supporting the survival of this anaerobe in the CF lung-relevant model.ImportancePolymicrobial interactions impact disease outcomes in pwCF who suffer from chronic respiratory infections. Previous work established a CF-relevant polymicrobial community model that allows experimental probing of these microbial interactions to achieve a better understanding of the factors that govern the mechanisms by which CF lung microbes influence each other. In this study, we investigate the interaction betweenP. aeruginosaandP. melaninogenica, which are two highly prevalent and abundant CF lung microbes. We uncover a cross-feeding mechanism that requires the metabolism of mucin byP. melaninogenicato generate short-chain fatty acids that are cross-fed toP. aeruginosa, and into metabolized into metabolites which are then cross-fed back toP. melaninogenicato support the growth of this anaerobe.