Albright, C. | bioRxiv Science

bioRxiv2026

Aerotolerant Capacity of the Lung Commensal Prevotella melaninogenica

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.

microbiology↗

bioRxiv2025

Development of a basal media for carbon utilization assay and analysis of the starch utilization locus in Prevotella melaninogenica

Prevotella melaninogenica is a highly abundant member of the human respiratory microbiota, occupying a range of distinct niches from the oral cavity to the lower airways. Colonization within these nutrient diverse environments suggest a sophisticated metabolic system equipped to deal with large fluctuations in nutrient availability. However, the core physiology and metabolic profile of this bacteria remain largely uncharacterized. In this study, we developed a basal media conducive to assaying carbon utilization of P. melaninogenica and demonstrate the utilization of dietary carbohydrates with varied glycosidic bonds, including the starch mimic cyclodextrin. Furthermore, we identified the putative starch utilization system, highlighting the presence of three novel components which are absent from starch metabolism in the closely related Bacteroides genus. Together, these findings provide the first characterization of the nutritional profile and central metabolic capacity of P. melaninogenica, offering crucial insight into how this bacterium adapts to and thrives within ecologically distinct niches. IMPORTANCEThis work significantly advances our understanding of the metabolic capabilities of Prevotella melaninogenica, a common yet largely unexplored member of the respiratory microbiota. By mapping key aspects of its predicted starch utilization locus, we lay the foundation for future studies on microbial adaptation and persistence in the respiratory tract.

microbiology↗