Salmonella Pathogenicity Island 2 Is Expressed Prior to Penetrating the Intestine

Open Access
Publisher Website
Google Scholar
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. Typhoid fever is a disease caused by specific Salmonella strains and is a significant cause of mortality in many regions of the developing world. Following a person's ingestion of Salmonella, the bacteria initially colonize the intestine, which they subsequently breach to reside in immune cells of the liver and spleen. The ability to survive inside immune cells directly contributes to the ability of Salmonella to cause typhoid, and is conferred upon Salmonella by the so-called Salmonella pathogenicity island 2 (SPI-2) type III secretion system. Previous work has shown that while SPI-2 is specifically turned on inside host cells, it is not active when grown in typical laboratory medium. Owing to these facts, it has been hypothesized that Salmonella specifically turn on SPI-2 inside host cells after breaching the host intestine. The researchers developed a sensitive system in Salmonella to test this hypothesis using a mouse model of typhoid. Interestingly, SPI-2 was specifically turned on before Salmonella breached the intestine, suggesting that SPI-2, which is integral to virulence, is active in a preemptive fashion to allow Salmonella to survive within the immune system.

This publication has 42 references indexed in Scilit: