Abstract
The ability to successfully adapt to changing host conditions is crucial for full virulence of bacterial pathogens. Staphylococcus aureus has to cope with fluctuating oxygen concentrations during the course of infection. Hence, we studied the effect of oxygen on glucose metabolism in non-growing S. aureus COL-S cells by in vivo 13C-NMR. Glucose catabolism was probed at different oxygen concentrations in suspensions of cells grown aerobically (direct effects on metabolism) or anaerobically (transcriptional adjustment to oxygen deprivation). In aerobically-grown cells, the rate of glucose consumption diminished progressively with decreasing oxygen concentrations. Additionally, oxygen deprivation resulted in biphasic glucose consumption, with the second phase presenting a higher rate. The fructose-1,6-bisphosphate pool peaked while glucose was still abundant, but the transient maximum varied with the oxygen concentration. As oxygen became limiting mannitol/mannitol-1-phosphate were detected as products of glucose catabolism. Under anoxic conditions, accumulation of mannitol-1-phosphate ceased with the switch to higher glucose consumption rates, which implies the activation of a more efficient means by which NAD+ can be regenerated. The distribution of end-products deriving from glucose catabolism was dramatically affected by oxygen: acetate increased and lactate decreased with the oxygen concentration; ethanol was formed only anaerobically. Moreover, oxygen promoted the energetically favourable conversion of lactate into acetate, which was particularly noticeable under fully oxygenated conditions. Interestingly, under aerobiosis growing S. aureus cells also converted lactate to acetate, used simultaneously glucose and lactate as substrates for growth, and grew considerably well on lactate-medium. We propose that the efficient lactate catabolism may endow S. aureus with a metabolic advantage in its ecological niche.
Highlights
Staphylococcus aureus is a Gram-positive bacterium frequently found on the skin and in the nasal cavity of humans
Cultivation of S. aureus was performed in chemically defined medium (CDM) supplemented with glucose (65 mM), at 37uC, and without pH control, in shake flasks agitated at 200 rpm or rubber-stoppered standing bottles
S. aureus is a common resident of the human body, and an opportunistic pathogen responsible for a variety of diseases in humans that range in severity from mild to fatal
Summary
Staphylococcus aureus is a Gram-positive bacterium frequently found on the skin and in the nasal cavity of humans. With widespread bacterial antibiotic resistance, of which S. aureus is a paradigm due to its remarkable adaptive capacity, it is urgent to find new ways to combat staphylococcal infections. One such opportunity is offered by the recognition of overlapping networks between pathogenesis and basic physiology. Corroborating this view, a number of studies have implicated central metabolic pathways in regulating or affecting staphylococcal virulence [3,4,5,6,7]. Elucidation of the underlying metabolic and regulatory networks involved is mandatory for an in-depth understanding of staphylococcal pathogenesis
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