Biology subjects

El Hafi, B.

Publications and source records attributed to El Hafi, B..

2 recordsLinked to original sources

bioRxiv2024

Pseudomonas aeruginosa supports the survival of Prevotella melaninogenica in a cystic fibrosis lung polymicrobial community through metabolic cross-feeding

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 in vitro CF-relevant polymicrobial community model composed of P. aeruginosa, S. aureus, S. sanguinis, and P. melaninogenica. P. melaninogenica cannot survive in monoculture in this model. In this study, we leverage this model to investigate the interactions between P. aeruginosa and P. melaninogenica, allowing us to understand the mechanisms by which the two microbes interact to support the growth of P. melaninogenica specifically in the context of the polymicrobial community. We demonstrate a cross-feeding mechanism whereby P. melaninogenica metabolizes mucin into short-chain fatty acids that are in turn utilized by P. aeruginosa and converted into metabolites (succinate, acetate) that are cross-fed to P. 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 between P. aeruginosa and P. melaninogenica, which are two highly prevalent and abundant CF lung microbes. We uncover a cross-feeding mechanism that requires the metabolism of mucin by P. melaninogenica to generate short-chain fatty acids that are cross-fed to P. aeruginosa, and into metabolized into metabolites which are then cross-fed back to P. melaninogenica to support the growth of this anaerobe.

microbiology↗

bioRxiv2024

DPR-MEDIATED H2O2 RESISTANCE CONTRIBUTES TO STREPTOCOCCI SURVIVAL IN A CYSTIC FIBROSIS AIRWAY MODEL SYSTEM

The cystic fibrosis (CF) lung environment is conducive to the colonization of bacteria as polymicrobial biofilms, which are associated with poor clinical outcomes for persons with CF (pwCF). Streptococcus spp. is highly prevalent in the CF airway, but its role in the CF lung microbiome is poorly understood. Some studies have shown Streptococcus spp. to be associated with better clinical outcomes for pwCF, while others show that high abundance of Streptococcus spp. is correlated with exacerbations. Our lab previously reported a polymicrobial culture system consisting of four CF-relevant pathogens that can be used to study microbial behavior in a more clinically relevant setting. Here, we use this model system to identify genetic pathways that are important for Streptococcus sanguinis survival in the context of the polymicrobial community. We identified genes related to reactive oxygen species (ROS) as differentially expressed in S. sanguinis monoculture versus growth of this microbe in the mixed community. Genetic studies identified Dpr as important for S. sanguinis survival in the community. We show that Dpr, a DNA binding ferritin-like protein, and PerR, a peroxide-responsive transcriptional regulator of Dpr, are important for protecting S. sanguinis from phenazine-mediated toxicity in co-culture with P. aeruginosa and when exposed to ROS, both of which mimic the CF lung environment. Characterizing such interactions in a clinically relevant model system contributes to our understanding of microbial behavior in the context of polymicrobial biofilm infections. IMPORTANCEStreptococcus spp. is recognized as a highly prevalent pathogen in CF airway infections. However, its role in clinical outcomes for pwCF is poorly understood. Here, we leverage a polymicrobial community system previously developed by our group to model CF airway infections as a tool to investigate a Pseudomonas-Streptococcus interaction involving ROS. We show that protection against ROS is required for S. sanguinis survival in a clinically relevant polymicrobial system. Using this model system to study interspecies interactions contributes to our broader understanding of the complex role of Streptococcus spp. in the CF lung.

microbiology↗