Epidemiological characteristics and co-occurrence patterns of Rothia species and respiratory pathogens: from population surveillance to mechanistic insights

Background Rothia is an oral commensal bacterium increasingly detected in the respiratory tract, and recent studies have highlighted changes in its abundance in respiratory infections.Objective This study aimed to investigate the species distribution of Rothia, its co-occurrence with respiratory pathogens, and the immune alterations associated with Rothia co-infection in respiratory infections.Design We developed real-time PCR to differentiate R. aeria, R. dentocariosa, and R. mucilaginosa. Sputum samples from 447 hospitalized patients were tested for 35 respiratory pathogens and three Rothia species using customized TaqMan Array Card. Co-infection murine models were established.Results All three Rothia species were frequently detected (39.4% to 72.3%). R. mucilaginosa showed positive associations with SARS-CoV-2 among patients with respiratory symptoms (odds ratio 4.0, p < 0.0001) or pneumonia (OR 2.7, p = 0.019) and influenza A virus (IAV; OR 8.4, p = 0.004) in patients with pneumonia during an influenza season, but was negatively associated with Klebsiella pneumoniae (OR 0.3, p < 0.05). These inverse associations were confirmed in murine models. Increased mortality and bacterial burden were observed in IAV and R. mucilaginosa co-infection, while K. pneumoniae and R. mucilaginosa co-infection was attenuated. Both models showed increased neutrophils. Functionally, IAV co-infection impaired bactericidal activity whereas prior K. pneumoniae exposure enhanced bacterial clearance.Conclusions This study uncovers distinct pathogen associations of Rothia in respiratory infections, which may provide evidence for their roles in shaping disease outcomes.