Aerotolerant Capacity of the Lung Commensal Prevotella melaninogenica

Abstract

Prevotella melaninogenica is a core member of the human oral and respiratory microbiomes, often representing more than 10% of microbial populations in both healthy and diseased lungs. Despite its prevalence in these oxygenated environments, P. melaninogenica has been historically classified as a strict obligate anaerobe, ostensibly unable to survive oxygen concentrations exceeding 0.05%. This creates a fundamental biological paradox, as the organism consistently persists in the lower respiratory tract where oxygen levels reach higher than what is tolerated by obligate anaerobes. In this study, we resolve this contradiction by evaluating the growth and tolerance of P. melaninogenica across intermediate oxygen concentrations of 2%, 5%, and 8%. Contrary to the long-standing classification, we demonstrate that P. melaninogenica maintains growth at 2% and 5% oxygen- a level significantly higher than previously reported for the genus- and exhibits robust aerotolerance in 21% O2. Transcriptional profiling via RNA-sequencing reveals that this survival is likely driven by the robust expression of oxidative stress defense and DNA repair machinery. Ultimately, these results provide the first evidence of the specialized mechanisms that enable Prevotella melaninogenica to adapt to and colonize the respiratory tract, providing a clearer understanding of its persistence in oxygen-exposed human niches. IMPORTANCEThis study provides a correction to the 100-year-old classification of Prevotella melaninogenica as a strict obligate anaerobe. We demonstrate that this key member of the human microbiome is capable of robust growth under oxygen levels previously thought to be lethal. By identifying transcriptional responses associated with growth and survival, we predict how Prevotella melaninogenica dominates the oxygenated niches of the respiratory tract. This work reveals the putative mechanisms driving the adaptive evolution of Prevotella melaninogenica and its role in human airway ecology.