Regulation of Oxidative Stress–Related Genes Implicated in the Establishment of Opportunistic Infections by Bacteroides Fragilis

Most of the microorganisms that inhabit the human gastrointestinal tract are strict anaerobic bacteria. These bacteria reach densities of up to 1014 cells per gram of feces and collectively outnumber our own cells by a factor of 10. Most of the bacterial species that live in our guts are harmless, and they actually contribute to our health in several ways. Some of these species, though, can turn against their hosts and cause opportunistic infections. These events are usually preceded by some change in the gut homeostasis, such as a rupture of the intestinal epithelia, which allow bacteria to penetrate deeper tissues. The gut bacteria Bacteroides fragilis is an important opportunistic pathogen and is the strict anaerobic bacteria most commonly isolated from human infections. Human tissues have high oxygen concentrations, in contrast to the anaerobic environment of the intestinal lumen. To survive in these environments, B. fragilis must mount a robust oxidative stress response (OSR), including changes in the expression of an extensive number of genes. Here, we review studies that elucidate the genetic mechanisms used by B. fragilis to control the expression of genes responsible for OSR. The best characterized of those regulators is the global regulator OxyR, which controls the expression of genes important for resistance to hydrogen peroxide. We also discuss the role of recently described regulators with homology to the multiple antibiotic resistance repressors (MarR) family and the Ferric uptake regulator (Fur), which establishes a link between iron storage and OSR.