How Oxygen Shapes Lactate Metabolism in Staphylococcus aureus: Insights from In Vivo NMR Original paper

What was studied?

This original research article investigated how varying oxygen concentrations affect glucose metabolism and specifically the utilization of lactate in Staphylococcus aureus. Using in vivo ^13C-NMR spectroscopy, the authors dissected metabolic responses by probing glucose catabolism in dense suspensions of S. aureus under differing oxygen conditions: fully aerobic, semi-aerobic, and anaerobic. The study focused on both direct effects of oxygen on metabolism (by using aerobically grown cells) and transcriptional adaptation to oxygen deprivation (by using anaerobically grown cells). The researchers examined substrate consumption rates, intracellular and extracellular metabolite pools, the emergence of metabolic intermediates, and the distribution of fermentation end-products. The goal was to clarify how oxygen availability modulates central carbon metabolism and to explore the capacity of S. aureus to utilize lactate, an abundant metabolite in host environments, especially under aerobic conditions.

Who was studied?

The study was performed exclusively on Staphylococcus aureus COL-S, a methicillin-sensitive derivative of the well-characterized COL strain. The experiments used laboratory-grown, non-growing (resting) cell suspensions for metabolic flux analyses, as well as actively growing cultures for growth and substrate utilization studies. The bacterial suspensions were prepared from cells cultivated under defined aerobic or anaerobic conditions to distinguish between immediate metabolic effects of oxygen and longer-term transcriptional adjustments. No human or animal subjects were involved; all findings are based on in vitro bacterial models.

Most important findings

The study revealed several key insights into S. aureus central metabolism under different oxygen availabilities. Under fully aerobic conditions, S. aureus consumed glucose at the fastest rate, primarily producing acetate and lactate, with acetate predominating as oxygen increased. As oxygen was limited, glucose consumption slowed, and lactate became the major end-product, with ethanol forming only under strict anaerobiosis. An important and novel observation was the marked ability of S. aureus to metabolize lactate to acetate under aerobic conditions—a process that was oxygen-dependent. This aerobic lactate utilization was confirmed both in non-growing and growing cells: S. aureus grew robustly using lactate as the sole carbon source and consumed lactate and glucose simultaneously when both were present, with a significant shift toward acetate production. The study also identified transient accumulation of mannitol/mannitol-1-phosphate under oxygen limitation, suggesting alternative NAD+ regeneration strategies. These findings highlight the metabolic flexibility of S. aureus and the impact of oxygen on its ability to switch between fermentation and respiration, as well as its capacity to exploit lactate—an abundant host metabolite—particularly in oxygen-rich environments.

Key implications

This work expands the understanding of S. aureus metabolic adaptability, with direct clinical and microbiome research relevance. The demonstration that S. aureus efficiently catabolizes lactate in the presence of oxygen suggests a metabolic advantage in oxygenated host niches (such as skin and nasal cavity), where lactate is often produced by commensal bacteria. This metabolic trait may facilitate S. aureus colonization and persistence by allowing it to exploit resources inaccessible to many competitors. The ability to switch to lactate utilization and its association with acetate production under aerobic conditions should be considered a key metabolic feature of S. aureus. These insights may inform future therapeutic strategies targeting metabolic pathways essential for S. aureus survival in diverse host environments.