Abstract
Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that causes disease in mice that resembles human typhoid. Typhoid pathogenesis consists of distinct phases in the intestine and a subsequent systemic phase in which bacteria replicate in macrophages of the liver and spleen. The type III secretion system encoded by Salmonella pathogenicity island 2 (SPI-2) is a major virulence factor contributing to the systemic phase of typhoid pathogenesis. Understanding how pathogens regulate virulence mechanisms in response to the environment, including different host tissues, is key to our understanding of pathogenesis. A recombinase-based in vivo expression technology system was developed to assess SPI-2 expression during murine typhoid. SPI-2 expression was detectable at very early times in bacteria that were resident in the lumen of the ileum and was independent of active bacterial invasion of the epithelium. We also provide direct evidence for the regulation of SPI-2 by the Salmonella transcription factors ompR and ssrB in vivo. Together these results demonstrate that SPI-2 expression precedes penetration of the intestinal epithelium. This induction of expression precedes any documented SPI-2-dependent phases of typhoid and may be involved in preparing Salmonella to successfully resist the antimicrobial environment encountered within macrophages.
Highlights
Salmonella is a Gram-negative bacterial pathogen that causes substantial morbidity and mortality worldwide
Once Salmonella has penetrated the intestinal epithelium, the systemic phase of typhoid begins by dissemination from the intestine via the lymphatics followed by colonization of macrophages of the liver and spleen [4,5]
The high degree of sensitivity of Recombinase-based in vivo expression technology (RIVET) was deemed important for the study of the monocopy expression level of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (T3SS)
Summary
Salmonella is a Gram-negative bacterial pathogen that causes substantial morbidity and mortality worldwide. Human-adapted serovars cause typhoid, a systemic and lifethreatening infection, while non-human-adapted serovars commonly cause enteritis. Following ingestion of contaminated food or water, the pathogenesis of both typhoid and Salmonella enteritis begins with an intestinal phase, while only typhoid progresses to a systemic phase. The intestinal phase of typhoid involves colonization of the intestine and penetration of the intestinal epithelium through two separate mechanisms. The first involves active bacterial invasion [1], and the second involves passive uptake of Salmonella during dendritic cell (DC) sampling of luminal microflora [2,3]. Once Salmonella has penetrated the intestinal epithelium, the systemic phase of typhoid begins by dissemination from the intestine via the lymphatics followed by colonization of macrophages of the liver and spleen [4,5]. Much of our understanding of typhoid pathogenesis has come from mice infected with S. enterica serovar Typhimurium, which models human typhoid in several respects
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