Metabolic strategies that enable oral commensal persistence in a lower airway environment

Chronic respiratory diseases such as bronchiectasis and cystic fibrosis are marked by persistent infection and inflammation, with oral bacteria increasingly recognized as active contributors. Among these, <i>Neisseria</i> species, typically considered health-associated commensals, are frequently detected in the lower airway, yet little is known about how they persist in this hostile environment. Here, we identify key metabolic pathways that support the survival of <i>Neisseria mucosa</i> in sputum-like media, including nitrate respiration, a pathway closely linked to inflammation. We also show that <i>N. mucosa</i> exhibits enhanced antibiotic resistance under these conditions, underscoring the need to study microbial physiology in host-relevant contexts. Finally, we demonstrate that a selective inhibitor of nitrate respiration suppresses <i>N. mucosa</i> growth in sputum-like but not standard media, revealing a context-specific vulnerability. These findings suggest that targeting inflammation-compatible metabolic pathways may inform new, non-antibiotic approaches for managing chronic respiratory diseases.