The Bacteroides fragilis transcriptome response to oxygen and H₂O₂: the role of OxyR and its effect on survival and virulence

Abstract

SummaryThe intestinal anaerobic symbiont, Bacteroides fragilis, is highly aerotolerant and resistant to H2O2. Analysis of the transcriptome showed that expression of 45% of the genome was significantly affected by oxidative stress. The gene expression patterns suggested that exposure to oxidative stress induced an acute response to rapidly minimize the immediate effects of reactive oxygen species, then upon extended exposure a broad metabolic response was induced. This metabolic response induced genes encoding enzymes that can supply reducing power for detoxification and restore energy-generating capacity. An integral aspect of the metabolic response was downregulation of genes related to translation and biosynthesis which correlated with decreased growth and entry into a stationary phase-like growth state. Examination of oxyR mutants showed that they were impaired for the acute response and they induced the expanded metabolic response with only minimal exposure to stress. The oxyR mutants were more sensitive to oxidants in vitro and in vivo they were attenuated in an intra-abdominal abscess infection model. Aerotolerance and resistance to oxidative stress are physiological adaptations of B. fragilis to its environment that enhance survival in extra-intestinal sites and promote opportunistic infections.

Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections

“…B. fragilis 638R was the WT strain used for genetic analyses. Bacteroides strains were grown in an anaerobic chamber in brain heart infusion broth supplemented with hemin and cysteine (BHIS) (10). Rifampicin (20 μg/mL), gentamicin (100 μg/mL), erythromycin (10 μg/mL), and tetracycline (5 μg/mL) were added for the selection of antibiotic resistance markers.…”

Peroxide‐Sensing Transcriptional Regulators in Bacteria

“…OxyR also upregulates the expression of OxyS, a small regulatory RNA that integrates peroxide stress with general stress pathways (34,122). Although there are significant differences, the OxyR regulons of other organisms tend to include similar classes of genes (39,82,96,104,116).…”

“…This is perhaps best illustrated by the peroxide-sensing regulators MgrA and SarZ in S. aureus, which have evolved to orchestrate the adaptive shift necessary to promote growth within a host in response to peroxide (5,53). Although they are viewed primarily as modulators of the oxidative stress response, OxyR (64,104), PerR (35,48,91,117), and OhrR (3) have all been shown to be required for virulence in at least one experimental system. In the case of OxyR and PerR, their effect on virulence is not solely related to the regulation of oxidative stress defense genes.…”

Thioredoxin system – a novel therapeutic target

“…This feature is allowed by large number of genes, which are expressed in aerobic conditions, including the genes for the Trx (Sund et al 2008). Entamoeba histolytica affecting amoebic dysentery or amoebic liver abscess in humans and primates also belongs to the anaerobic parasites, which lack the glutathione system and an unusual form of glutathionetrypanothione (Ariyanayagam and Fairlamb 1999;Ryan and Ray 2004).…”