Effect of Oxygen on Glucose Metabolism: Utilization of Lactate in Staphylococcus Aureus as Revealed by In Vivo NMR Studies Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Microbes
Microbes
Microbes, short for microorganisms, are tiny living organisms that are ubiquitous in the environment, including on and inside the human body. They play a crucial role in human health and disease, functioning within complex ecosystems in various parts of the body, such as the skin, mouth, gut, and respiratory tract. The human microbiome, which is […]
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was studied?
This study investigated the effect of oxygen availability on glucose metabolism and lactate utilization in Staphylococcus aureus (strain COL-S) using in vivo ¹³C-NMR spectroscopy. The goal was to characterize metabolic shifts and intracellular metabolite dynamics under aerobic, semi-aerobic, and anaerobic conditions in non-growing S. aureus cells, and to determine whether lactate could serve as a carbon source for growth. Glucose metabolism was evaluated in both aerobically and anaerobically pre-grown cells, enabling the dissection of direct metabolic regulation from transcriptional adaptation.
Who was studied?
The experimental organism was Staphylococcus aureus COL-S, a methicillin-sensitive derivative of the MRSA strain COL. Cells were cultured in a chemically defined medium optimized for NMR studies. Both aerobically and anaerobically grown cells were examined to distinguish immediate metabolic effects from longer-term transcriptional changes induced by oxygen levels.
Most important findings
The study revealed that oxygen availability fundamentally alters the central carbon metabolism of S. aureus. Under fully oxygenated conditions, S. aureus preferentially oxidized glucose to acetate and lactate, and later converted lactate to acetate, reflecting active respiratory metabolism. As oxygen became limited, the bacteria shifted toward a fermentative profile, accumulating more lactate and producing mannitol/mannitol-1-phosphate (Mtl/Mtl1P) as electron sinks to regenerate NAD⁺.
In fully anoxic conditions, glucose metabolism was biphasic: a slow initial phase was followed by a faster consumption phase, suggesting an adaptive metabolic switch. FBP (fructose-1,6-bisphosphate) and Mtl1P peaks marked the transition, after which NAD⁺ regeneration pathways appeared to improve. End-products under anaerobiosis included lactate (major), acetate, ethanol, and 2,3-butanediol. Notably, S. aureus demonstrated an unexpected capacity to catabolize lactate aerobically, converting it efficiently to acetate via pyruvate, thereby sustaining NAD⁺ balance and ATP production through substrate-level phosphorylation.
The study confirmed that S. aureus could grow robustly on lactate alone under aerobic conditions, without a sugar source, and utilized glucose and lactate simultaneously without catabolite repression. These results position lactate as a viable and underappreciated carbon source for S. aureus, especially in oxygen-rich host niches like the skin and nasal cavity, where it may outcompete fermentative commensals.
From a microbiome signatures perspective, this metabolic adaptability of S. aureus—particularly its efficient use of lactate—is a critical trait for ecological fitness and niche dominance. In microbial clustering models, lactate metabolism may distinguish S. aureus from commensals that lack this capability, forming a basis for identifying S. aureus as a Major Microbial Association (MMA) in certain pathologies.
Greatest implications of this study
The capacity of S. aureus to efficiently utilize lactate aerobically confers a competitive ecological advantage, enabling it to thrive in host niches with low carbohydrate availability but high lactate levels due to resident fermentative microbiota. This trait may underpin its success as both a commensal and a pathogen. The finding that S. aureus expresses both NAD⁺-dependent and potentially NAD⁺-independent lactate dehydrogenases adds a layer of complexity to its metabolic plasticity, potentially informing antimicrobial strategies that target lactate uptake and oxidation pathways. From a microbiome interventions standpoint, targeting lactate metabolism could be a novel approach to disrupting S. aureus colonization and virulence.