TheSalmonella entericaSerotype Typhimurium Effector Proteins SipA, SopA, SopB, SopD, and SopE2 Act in Concert To Induce Diarrhea in Calves

Abstract

Salmonella enterica serotype Typhimurium requires a functional type III secretion system encoded by Salmonella pathogenicity island 1 (SPI1) to cause diarrhea. We investigated the role of genes encoding secreted target proteins of the SPI1-associated type III secretion system for enteropathogenicity in calves. Salmonella serotype Typhimurium strains having mutations in sptP, avrA, sspH1, or slrP induced fluid secretion in the bovine ligated ileal loop model at levels similar to that of the wild type. In contrast, mutations in sipA, sopA, sopB, sopD, or sopE2 significantly reduced fluid accumulation in bovine ligated ileal loops at 8 h postinfection. A strain carrying mutations in sipA, sopA, sopB, sopD, and sopE2 (sipA sopABDE2 mutant) caused the same level of fluid accumulation in bovine ligated ileal loops as a strain carrying a mutation in sipB, a SPI1 gene required for the translocation of effector proteins into host cells. A positive correlation was observed between the severity of histopathological lesions detected in the ileal mucosa and the levels of fluid accumulation induced by the different mutants. After oral infection of calves, the Salmonella serotype Typhimurium sipAsopABDE2 mutant caused only mild diarrhea and was more strongly attenuated than strains having only single mutations. These data demonstrate that SipA, SopA, SopB, SopD, and SopE2 are major virulence factors responsible for diarrhea during Salmonella serotype Typhimurium infection of calves.

SipA, SopA, SopB, SopD and SopE2 effector proteins of Salmonella enterica serovar Typhimurium are synthesized at late stages of infection in mice

“…Like its homologue SopE, SopE2 contributes to the bacterial invasion of epithelial cells (Buchwald et al, 2002;, and has also been implicated in the pathogenesis of diarrhoea and enteritis in calves (Zhang et al, 2002). It is not clear whether this effect of SopE2 is related to its role in bacterial invasion or to some other function.…”

“…Earlier work has demonstrated a role for SopA in the Salmonella-induced movement of polymorphonuclear leukocytes across the intestinal epithelium (Wood et al, 2000) and shown that SopA acts in concert with other TTSS-1-secreted effector proteins (Zhang et al, 2002). More recently, Layton et al (2005) have reported that SopA localizes to mitochondria; the correlation of this fact with the role of SopA in virulence remains unknown.…”

“…resides (Patel & Galan, 2005). Absence of sopD leads to a reduction of both fluid secretion and inflammatory responses during infection (Jones et al, 1998;Zhang et al, 2002). In vitro experiments using HeLa cells have shown that the expression of sopD is maintained at later stages of infection, suggesting that this effector may also play a role in systemic infection of the host (Brumell et al, 2003).…”

“…Although SopB, SopD and SopE2 are clearly involved in host cell invasion (Raffatellu Proteins from internalized bacteria were extracted as described in Methods The role of SopB in the inflammatory response and in fluid secretion in the infected ileum has been discussed earlier (Zhang et al, 2002). Furthermore, SopB could also participate in the development of murine salmonellosis after invasion and during the late stages of the disease.…”

Molecular insights into farm animal and zoonoticSalmonellainfections

“…The T3SS-1 effector proteins SipA, SopA, SopB, SopD and SopE/E2 act in concert to induce enteritis in bovine ileal loops (Wood et al 1996(Wood et al , 2000Jones et al 1998;Zhang et al 2002b). SopA is a HECTlike E3 ubiquitin ligase that influences neutrophil transmigration across epithelia, possibly by ubiquitination of cellular and bacterial factors involved in inflammation (Zhang et al 2006).…”