A Commensal Streptococcus Dysregulates the Nitrosative Stress Response.

Chronic infections in the cystic fibrosis (CF) airway are composed of both pathogenic and commensal bacteria. However, chronic infections are the leading cause of lung deterioration in individuals with CF. Interestingly, oral commensals can translocate to the CF lung and their presence is associated with improved lung function, presumably due to their ability to antagonize . We have previously shown that one commensal, , produces hydrogen peroxide that reacts with nitrite to generate reactive nitrogen intermediates (RNI) which inhibit growth. In this study, we sought to understand the global impact of commensal-mediated RNI on the transcriptome. RNA sequencing analysis revealed that and nitrite-mediated RNI dysregulated expression of denitrification genes in a CF isolate of compared to when this isolate was only exposed to . Further, loss of a nitric oxide reductase subunit () rendered an acute isolate more susceptible to mediated RNI. Additionally, -mediated RNI inactivated aconitase activity. Lastly, we report that isolates recovered from CF individuals are uniquely hypersensitive to -mediated RNI compared to acute infection or environmental isolates. These findings illustrate that hinders the ability of to respond to RNI, which potentially prevents CF isolates from resisting commensal and host-induced RNI in the CF airway.