How does oxygen inhibit central metabolism in the obligate anaerobe Bacteroides thetaiotaomicron

The molecular basis of obligate anaerobiosis is not well established. Bacteroides thetaiotaomicron is an opportunistic pathogen that cannot grow in fully aerobic habitats. Because microbial niches reflect features of energy‐producing strategies, we suspected that aeration would interfere with its central metabolism. In anaerobic medium, this bacterium fermented carbohydrates to a mixture of succinate, propionate and acetate. When cultures were exposed to air, the formation of succinate and propionate ceased abruptly. In vitro analysis demonstrated that the fumarase of the succinate–propionate pathway contains an iron–sulphur cluster that is sensitive to superoxide. In vivo , fumarase activity fell to < 5% when cells were aerated; virtually all activity was recovered after extracts were chemically treated to rebuild iron–sulphur clusters. Aeration minimally affected the remainder of this pathway. However, aeration reduced pyruvate:ferredoxin oxidoreductase (PFOR), the first enzyme in the acetate fermentation branch, to 3% of its anaerobic activity. This cluster‐containing enzyme was damaged in vitro by molecular oxygen but not by superoxide. Thus, aerobic growth is precluded by the vulnerability of these iron–sulphur cluster enzymes to oxidation. Importantly, both enzymes were maintained in a stable, inactive form for long periods in aerobic cells; they were then rapidly repaired when the bacterium was returned to anaerobic medium. This result explains how this pathogen can easily recover from occasional exposure to oxygen.