African Salmonella enterica serovar Typhimurium ST313 isolates prevent reactive oxygen species production by human neutrophils via elevated PgtE expression.

A recently emerged Salmonella enterica serotype Typhimurium variant, ST313, is a frequent cause of bloodstream infections associated with high mortality rates in sub-Saharan Africa. While the interaction of ST313 strains with macrophages has been studied extensively, interactions with other innate immune effectors such as neutrophils have been largely ignored. We found that a subset of ST313 strains induces an attenuated neutrophil oxidative burst, which can facilitate increased bacterial survival within human neutrophils. The ST313 isolates that avoid triggering potent reactive oxygen species production by neutrophils express elevated levels of the protease PgtE. Increased pgtE expression promotes decreased complement deposition on S. Typhimurium and a concomitant increase in disseminated infection in mice. Our results show that high-level PgtE expression contributes to evasion of the neutrophil oxidative burst by S. Typhimurium, suggesting a possible mechanism contributing to invasive S. Typhimurium disease.IMPORTANCEThe S. enterica serotype Typhimurium omptin family protease PgtE has long been known to cleave complement factors bound to the bacterial surface, but a role for complement inactivation by PgtE in avoidance of serum bactericidal activity was found only for bacteria having rough lipopolysaccharide. Here we show that PgtE-mediated interference with the complement cascade helps evade the oxidative burst of human neutrophils. Our results suggest a mechanism by which increased expression of this protease by S. Typhimurium strains associated with severe bloodstream infection promotes evasion of the innate immune response by S. Typhimurium.