Salmonella detoxifying enzymes are sufficient to cope with the host oxidative burst

Abstract

SummaryThe oxidative burst produced by the NADPH oxidase (Phox) is an essential weapon used by host cells to eradicate engulfed pathogens. In Salmonella typhimurium, oxidative stress resistance has been previously proposed to be mediated by the pathogenicity island 2 type III secretion system (T3SS-2), periplasmic superoxide dismutases and cytoplasmic catalases/ peroxidases. Here, we fused an OxyR-dependent promoter to the gfp to build the ahpC-gfp transcriptional fusion. This reporter was used to monitor hydrogen peroxide levels as sensed by Salmonella during the course of an infection. We showed that the expression of this fusion was under the exclusive control of reactive oxygen species produced by the host. The ahpCgfp expression was noticeably modified in the absence of bacterial periplasmic superoxide dismutases or cytoplasmic catalases/peroxidases. Surprisingly, inactivation of the T3SS-2 had no effect on the ahpC-gfp expression. All together, these results led to a model in which Salmonella resistance relies on its arsenal of detoxifying enzymes to cope with Phoxmediated oxidative stress.

Direct measurement of oxidative and nitrosative stress dynamics in Salmonella inside macrophages

“…Unable to measure differences in oxidative stress between WT and SPI-2-deficient S. Typhimurium during infection of macrophages and mice, the authors concluded that Salmonella detoxifying enzymes are sufficient to cope with the host oxidative burst and there is no role for the SPI-2 system in evasion strategies (7). These seemingly conflicting results created some confusion about the role of SPI-2 in ROS evasion strategies (8,9).…”

“…A more recent attempt to indirectly measure oxidative stress inside S. Typhimurium used induction of an oxidation sensitive ahpCp-GFP transcriptional fusion (7). Unable to measure differences in oxidative stress between WT and SPI-2-deficient S. Typhimurium during infection of macrophages and mice, the authors concluded that Salmonella detoxifying enzymes are sufficient to cope with the host oxidative burst and there is no role for the SPI-2 system in evasion strategies (7).…”

“…Typhimurium (S. Typhimurium), which is a major cause of gastroenteritis and some systemic diseases, remains inside a specific Salmonella-containing vacuole (SCV), where it injects bacterial effector proteins directly into the host cell through a type III secretion system (T3SS). A specific set of type III effectors associated with a Salmonella pathogenicity island (SPI), known as SPI-2 effectors, have been implicated in ROS and RNS evasion strategies (5,6); however, the relationship between SPI-2 and oxidative stress evasion is a contentious topic after a recent study concluded that the contribution of SPI-2 to Salmonella pathogenesis is unrelated to its interaction with oxidative stress (7). Inadequate analytic tools for directly measuring ROS/RNS and rapid fluctuations due to the short-lived nature of ROS/RNS have also contributed to poor reproducibility in the studies of ROS and RNS evasion strategies (1,8,9).…”

Biotin sulfoxide reductase contributes to oxidative stress tolerance and virulence in Salmonella enterica serovar Typhimurium

“…Bacteria detoxify ROS using superoxide dismutases, catalases and peroxiredoxin-type peroxidases (peroxiredoxins) (Aussel et al, 2011;Fang et al, 1999;Hébrard et al, 2009;Horst et al, 2010;Kim et al, 2010;Krishnakumar et al, 2004;Uzzau et al, 2002). Besides detoxification, repair of damage caused by ROS is crucial.…”

Reactive oxygen species (ROS) generation, impacts on tissue oxidation and dietary management of non-communicable diseases: A review

“…A rare variant of chronic granulomatous disease (CGD); an inherited disorder where phagocytes are unable to kill certain bacteria and fungi produced significant amounts of singlet oxygen but very little superoxide and neutrophils provided a useful model to check oxidative burst (Aussel et al, 2011;Slauch, 2011). It was found out that superoxide (SOD) mutant mice as compared with wild mice, singlet oxygen was consumed by some reaction that did not result in the production of hydrogen peroxide (Aussel et al, 2011). The results from this study clearly points to the validity of the existence of a potent oxidant responsible for the reactions.…”