[Show abstract][Hide abstract] ABSTRACT: Bacteroides fragilis can replicate in atmospheres containing ≤0.05% oxygen, but higher concentrations arrest growth by an unknown mechanism. Here we show that inactivation of a single gene, oxe (i.e., oxygen enabled) in B. fragilis allows for growth in concentrations as high as 2% oxygen while increasing the tolerance of this organism to room air. Known components of the oxidative stress response including the ahpC, kat, batA-E, and tpx genes were not individually important for microaerobic growth. However, a Δoxe strain scavenged H(2)O(2) at a faster rate than WT, indicating that reactive oxygen species may play a critical role in limiting growth of this organism to low-oxygen environments. Clinical isolates of B. fragilis displayed a greater capacity for growth under microaerobic conditions than fecal isolates, with some encoding polymorphisms in oxe. Additionally, isolation of oxygen-enabled mutants of Bacteroides thetaiotaomicron suggests that Oxe may mediate growth arrest of other anaerobes in oxygenated environments.
Proceedings of the National Academy of Sciences 07/2012; 109(30):12153-8. DOI:10.1073/pnas.1203796109 · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite the detrimental role that endogenously generated reactive oxygen species (ROS) may play in bacteria exposed to aerobic environments, very few sources of ROS have been identified in vivo. Such studies are often precluded by the presence of efficient ROS-scavenging pathways, like those found in the aerotolerant anaerobe Bacteroides fragilis. Here we demonstrate that deletion of the genes encoding catalase (Kat), alkylhydroperoxide reductase (AhpC) and thioredoxin-dependent peroxidase (Tpx) strongly inhibits H(2)O(2) detoxification in B. fragilis, thereby allowing for the quantification of ROS production. Exogenous fumarate significantly reduced H(2)O(2) production in a ΔahpCΔkatΔtpx B. fragilis strain, as did deletion of fumarate reductase subunit c (frdC). Deletion of frdC also increased the aerotolerance of a strain lacking superoxide dismutase, indicating that fumarate reductase is a major contributor to ROS formation in B. fragilis exposed to oxygen.