DPR-MEDIATED H2O2RESISTANCE CONTRIBUTES TO STREPTOCOCCI SURVIVAL IN A CYSTIC FIBROSIS AIRWAY MODEL SYSTEM

Abstract

ABSTRACTThe 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).Streptococcusspp. is highly prevalent in the CF airway, but its role in the CF lung microbiome is poorly understood. Some studies have shownStreptococcusspp. to be associated with better clinical outcomes for pwCF, while others show that high abundance ofStreptococcusspp. 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 forStreptococcus sanguinissurvival in the context of the polymicrobial community. We identified genes related to reactive oxygen species (ROS) as differentially expressed inS. sanguinismonoculture versus growth of this microbe in the mixed community. Genetic studies identified Dpr as important forS. sanguinissurvival 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 protectingS. sanguinisfrom phenazine-mediated toxicity in co-culture withP. aeruginosaand 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.IMPORTANCEStreptococcusspp. 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 aPseudomonas-Streptococcusinteraction involving ROS. We show that protection against ROS is required forS. sanguinissurvival in a clinically relevant polymicrobial system. Using this model system to study interspecies interactions contributes to our broader understanding of the complex role ofStreptococcusspp. in the CF lung.