Pathogenicity island excision during an infection by Salmonella enterica serovar Enteritidis is required for crossing the intestinal epithelial barrier in mice to cause systemic infection

Abstract

Pathogenicity island excision is a phenomenon that occurs in several Salmonella enterica serovars and other members of the family Enterobacteriaceae. ROD21 is an excisable pathogenicity island found in the chromosome of S. Enteritidis, S. Dublin and S. Typhi among others, which contain several genes encoding virulence-associated proteins. Excision of ROD21 may play a role in the ability of S. Enteritidis to cause a systemic infection in mice. Our previous studies have shown that Salmonella strains unable to excise ROD21 display a reduced ability to colonize the liver and spleen. In this work, we determined the kinetics of ROD21 excision in vivo in C57BL/6 mice and its effect on virulence. We quantified bacterial burden and excision frequency in different portions of the digestive tract and internal organs throughout the infection. We observed that the frequency of ROD21 excision was significantly increased in the bacterial population colonizing mesenteric lymph nodes at early stages of the infective cycle, before 48 hours post-infection. In contrast, excision frequency remained very low in the liver and spleen at these stages. Interestingly, excision increased drastically after 48 h post infection, when intestinal re-infection and mortality begun. Moreover, we observed that the inability to excise ROD21 had a negative effect on S. Enteritidis capacity to translocate from the intestine to deeper organs, which correlates with an abnormal transcription of invA in the S. Enteritidis strain unable to excise ROD21. These results suggest that excision of ROD21 is a genetic mechanism required by S. Enteritidis to produce a successful invasion of the intestinal epithelium, a step required to generate systemic infection in mice.

Salmonella Effector SpvB Disrupts Intestinal Epithelial Barrier Integrity for Bacterial Translocation

“…After oral infection, nontyphoidal Salmonella usually remain localized to intestinal tissues for survival and replication, and sometimes manage to pass through intestinal barrier for systemic spread via both transcellular and paracellular pathways. As an effective physical barrier against enteric pathogens, intestinal epithelial barrier plays a key role in regulating the localized or systemic infection of nontyphoidal Salmonella (Hu et al, 2016;Pardo-Roa et al, 2019). As expected, Salmonella have evolved intricate strategies to overcome or manipulate mechanisms of the intestinal epithelial barrier integrity.…”

Horizontally Acquired Homologs of Xenogeneic Silencers: Modulators of Gene Expression Encoded by Plasmids, Phages and Genomic Islands

“…The excision process is likely promoted by the products of the genes SEN1970 and SEN1998, which are predicted to encode a tyrosine recombinase and a putative recombination directionality factor, respectively. Indeed, compared with the wildtype strain, the fraction of bacteria with the excised island is reduced in the ∆SEN1970::FRT and the ∆SEN1970::FRT ∆SEN1998::FRT population [50,105,107].…”

“…ROD21 is also an excisable island, a feature that has reached a special relevance due to its role in the virulence of Salmonella ser. Enteritidis since different mutant strains, with a reduced excision capacity, show a reduced colonization of the liver and spleen of infected mice [81,105]. The DRSs that flank ROD21 participate in the site-specific recombination reaction that excises the island and produces a circular form of the element [81,106].…”

“…Recent findings show that the Salmonella ser. Enteritidis ∆SEN1970::FRT ∆SEN1998::FRT mutant, which have a reduced expression of several ROD21-encoded genes, also have a significantly increased expression of invA, a gene encoding a structural component of the T3SS-1 [105]. invA, as well as other SPI-1-encoded genes, are upregulated by proteins also encoded by SPI-1 which are, at the same time, negatively regulated by H-NS [114], raising the possibility that the observed link between the two pathogenicity islands could be the result of the H-NSB ROD21 protein interacting with H-NS or the H-NS binding sites within SPI-1.…”

Detection of invA virulence gene of multidrug-resistant Salmonella species isolated from the cloacal swab of broiler chickens in Blitar district, East Java, Indonesia

“…In Salmonella isolates, invA was located in SPI-1, which plays an extremely important role in the invasion of host epithelial cells. This gene is highly specific for most Salmonella species [44,45]. Salmonella spp.…”