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Abstract: The intestinal opportunistic pathogen Bacteroides fragilis is among the most aerotolerant species of strict anaerobic bacteria and survives exposure to atmospheric oxygen for up to 72h. Under these circumstances, a strong oxygen stress response (OSR) mechanism is activated and the expression of as much as 45% of B. fragilis genes is altered. One of the most important regulators of this response is the product of the oxyR gene, but other regulation systems are in place during the OSR. The MarR family of transcriptional regulators has been shown to control several physiological events in bacteria, including response to stress conditions. In B. fragilis, at least three homologs of MarR regulators are present, one of which, bmoR, is upregulated during oxidative stress independently of oxyR. In this study, we demonstrate that the inactivation of the bmoR gene in B. fragilis diminishes its ability to withstand oxidative stress caused either by exposure to atmospheric oxygen or hydrogen peroxide. Recovery of growth rate on pre-oxidized media under anaerobiosis is slower than that observed in parental strain. Addition of hydrogen peroxide has a similar effect on the growth rate. Complementation of the mutant strain partially recovered the oxygen resistance phenotype, but the overexpression of the gene in the parental strain was also deleterious to a lesser extent. Our results indicate that BmoR has a role in the OSR in B. fragilis, particularly in the initial stages of oxygen exposure. [Copyright &y& Elsevier]

Abstract: Mammalian matrix metalloproteinases (MMPs) degrade collagen networks in extracellular matrices by cleaving collagen and its denatured form gelatin, and thus enhance migration of mammalian cells. The gastrointestinal pathogen Salmonella enterica survives and grows within host macrophages and dendritic cells, and can disseminate in the host by travelling within infected host cells. Here, we report that S. enterica serovar Typhimurium activates proMMP-9 (gelatinase B) secreted by human primary macrophages, and degrades gelatin after growth within J774A.1 murine macrophage-like cells. Both proMMP-9 activation and gelatin degradation were due to expression of the Salmonella surface protease PgtE. Following intraperitoneal infection in BALB/c mice, the amount of a pgtE deletion derivative was nearly ten-fold lower in the livers and spleens of mice than the amount of wild-type S. enterica, suggesting that PgtE contributes to dissemination of Salmonella in the host. PgtE belongs to the omptin family of bacterial β-barrel transmembrane proteases. The ortholog of PgtE in Yersinia pestis, Pla, which is central for bacterial virulence in plague, was poor in proMMP-9 activation and in gelatin degradation. To model the evolution of these activities in the omptin barrel, we performed a substitution analysis in Pla and genetically modified it into a PgtE-like gelatinase. Our results indicate that PgtE and Pla have diverged in substrate specificity, and suggest that Salmonella PgtE has evolved to functionally mimic mammalian MMPs. [Copyright &y& Elsevier]