Excision of an Unstable Pathogenicity Island in Salmonella enterica Serovar Enteritidis Is Induced during Infection of Phagocytic Cells

Abstract

The availability of the complete genome sequence of several Salmonella enterica serovars has revealed the presence of unstable genetic elements in these bacteria, such as pathogenicity islands and prophages. This is the case of Salmonella enterica serovar Enteritidis (S. Enteritidis), a bacterium that causes gastroenteritis in humans and systemic infection in mice. The whole genome sequence analysis for S. Enteritidis unveiled the presence of several genetic regions that are absent in other Salmonella serovars. These regions have been denominated “regions of difference” (ROD). In this study we show that ROD21, one of such regions, behaves as an unstable pathogenicity island. We observed that ROD21 undergoes spontaneous excision by two independent recombination events, either under laboratory growth conditions or during infection of murine cells. Importantly, we also found that one type of excision occurred at higher rates when S. Enteritidis was residing inside murine phagocytic cells. These data suggest that ROD21 is an unstable pathogenicity island, whose frequency of excision depends on the environmental conditions found inside phagocytic cells.

Microarray-Based Detection of Salmonella enterica Serovar Enteritidis Genes Involved in Chicken Reproductive Tract Colonization

“…The cluster contains a Toll/interleukin-1 receptor domain containing protein SEN1975 or TlpA that might suppress NF-B induction while it promotes host cell apoptosis (28,31,32). A tlpA mutant was defective in intracellular survival inside human THP1 macrophages, and mice infected with the tlpA mutant survived the challenge better compared to the wild type (32).…”

“…A tlpA mutant was defective in intracellular survival inside human THP1 macrophages, and mice infected with the tlpA mutant survived the challenge better compared to the wild type (32). ROD21 also comprises two putative type IV pilin proteins (SEN1976 and SEN1978), which might be linked to several functions, including motility, adhesion, and biofilm and bacterial aggregate formation, as well as invasion (28,31). Also, two conjugational transfer proteins (SEN1979 and SEN1980) and a histone-like nucleoid-structuring regulator (SEN1993) are located on ROD21, of which the latter was shown to be a homologue of the uropathogenic E. coli hnsT gene, which promotes the expression of virulence genes (31).…”

“…ROD21 also comprises two putative type IV pilin proteins (SEN1976 and SEN1978), which might be linked to several functions, including motility, adhesion, and biofilm and bacterial aggregate formation, as well as invasion (28,31). Also, two conjugational transfer proteins (SEN1979 and SEN1980) and a histone-like nucleoid-structuring regulator (SEN1993) are located on ROD21, of which the latter was shown to be a homologue of the uropathogenic E. coli hnsT gene, which promotes the expression of virulence genes (31). Nevertheless, a role for ROD21 in reproductive tract colonization could not be demonstrated since a ROD21 deletion mutant had the same colonization levels in this organ as the wild type after oral inoculation (29).…”

Bacterial Genome Instability

“…Sometimes a GI excises together with a part of or all of its surrounding tRNA, leading to the loss of this coding sequence (93). Interestingly, specific parts or a whole pathogenicity island can excise at a precise point of a pathological process to facilitate the next stage of an infection (as in Salmonella enterica serovar Enteritidis [111]). Following its excision, a GI can integrate into a different locus of the same chromosome or be transmitted to another cell by horizontal gene transfer (such as the 89K pathogenicity island in Streptococcus suis serotype 2 [112]).…”

Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars

“…While most of the SPIs are not likely to retain their mobility, the ability of some Salmonella genomic islands to excise and transfer has been demonstrated. This excision is also inducible for some regions upon exposure to host conditions, such as macrophage survival and oxidative stress (112).…”