A Commensal Streptococcus Dysregulates the Pseudomonas aeruginosa Nitrosative Stress Response
Year: 2022
Type: article
Abstract: Chronic infections in the cystic fibrosis (CF) airway are composed of both pathogenic and commensal bacteria. However, chronic Pseudomonas aeruginosa 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 P. aeruginosa. We have previously shown that one commensal, Streptococcus parasanguinis, produces hydrogen peroxide that reacts with nitrite to generate reactive nitrogen intermediates (RNI) which inhibit P. aeruginosa growth. In this study, we sought to understand the global impact of commensal-mediated RNI on the P. aeruginosa transcriptome. RNA sequencing analysis revealed that S. parasanguinis and nitrite-mediated RNI dysregulated expression of denitrification genes in a CF isolate of P. aeruginosa compared to when this isolate was only exposed to S. parasanguinis. Further, loss of a nitric oxide reductase subunit (norB) rendered an acute P. aeruginosa isolate more susceptible to S. parasanguinis-mediated RNI. Additionally, S. parasanguinis-mediated RNI inactivated P. aeruginosa aconitase activity. Lastly, we report that P. aeruginosa isolates recovered from CF individuals are uniquely hypersensitive to S. parasanguinis-mediated RNI compared to acute infection or environmental P. aeruginosa isolates. These findings illustrate that S. parasanguinis hinders the ability of P. aeruginosa to respond to RNI, which potentially prevents P. aeruginosa CF isolates from resisting commensal and host-induced RNI in the CF airway.
Institution: University of Alabama at Birmingham
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: National Science Foundation, National Institutes of Health, Heflin Center for Genomic Science, University of Alabama at Birmingham, Center for Clinical and Translational Science, University of Alabama at Birmingham, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Dental and Craniofacial Research, National Center for Advancing Translational Sciences
Awards: G133847405, G3389243587, G3913178333, UAB Predoctoral Training Program in Lung Diseases, G445220597, G4834669152, G5277000622, Inhibition of Streptococcus mutans by oral commensal streptococci and nitrie-mediated activity, G6188760114, Interactions between Pseudomonas aeruginosa and Streptococcus salivarius and effects on the host immune response, G694332062, G9000031784, G9000086830, G9000136463, LSAMP BD: University of Alabama at Birmingham-Alabama LSAMP Sustainability of Best Practices
OpenAlex ID: W4229458140