Salmonella enterica Serovar Senftenberg Human Clinical Isolates Lacking SPI-1

Abstract

Nontyphoidal Salmonella species cause gastrointestinal disease worldwide. The prevailing theory of Salmonella enteropathogenesis is that bacterial invasion of the intestinal epithelium is essential for virulence and that this requires the virulence-associated genomic region Salmonella pathogenicity island 1 (SPI-1). Recent studies of Salmonella enterica infection models have demonstrated that enterocolitis and diarrhea in mice and cows can occur independently of SPI-1. In this study, we sought to confirm whether two S. enterica serovar Senftenberg clinical isolates lacked genes essential for SPI-1 function. Two clinical strains were isolated and identified as being S. enterica serovar Senftenberg from four stool samples from a food-borne disease outbreak affecting seven individuals in Shenzhen, Guangdong Province, China, using conventional methods, pulsed-field gel electrophoresis and multilocus sequence typing. The possibility of coinfection with other potential bacteria or usual viruses was excluded. Two isolates were analyzed for the presence of invA, sipA, ssaR, sifA, and sopE2 by PCR and Southern blotting and were then assayed for the presence of SPI-1 by PCR and long-range PCR for fhlA-hilA, hilA-spaP, and spaP-invH and Southern blot analysis. A long-range PCR fragment from fhlA to mutS covering the 5 and 3 flanks of SPI-1 was also amplified from the two clinical isolates and sequenced. In addition, the two clinical isolates were assayed for enteroinvasiveness in vitro. Murine infection models were also examined. Biochemical tests and serotyping confirmed that the two clinical isolates are S. enterica serovar Senftenberg. However, they lacked genes critical for SPI-1 function but contained SPI-2 genes and were attenuated for the invasion of cultured intestinal epithelial cells. In conclusion, clinical S. enterica serovar Senftenberg strains isolated from a food-borne disease outbreak lack the invasion-associated locus SPI-1, indicating that SPI-1 is not essential for human gastroenteritis.

Heterogeneity of type III secretion system (T3SS)-1-independent entry mechanisms used by Salmonella Enteritidis to invade different cell types

“…For a long time it was assumed that cell invasion by Salmonella was only associated with its T3SS-1, which induces a Trigger mechanism. However, some studies have reported that Salmonella strains lacking SPI-1 are able to induce enterocolitis both in humans and in mouse and bovine models (Coombes et al, 2005;Hapfelmeier et al, 2005;Hu et al, 2008). The present study confirms that although T3SS-1 is the main in vitro Salmonella invasion factor for all the cell lines tested, T3SS-1-independent processes can play a not insignificant role.…”

“…However, several recent reports have suggested that Salmonella can be pathogenic without an active T3SS-1. For example, a Salmonella Senftenberg strain lacking T3SS-1 was isolated from a human clinical case and shown to be able to induce enterocolitis in a mouse model (Hu et al, 2008). Moreover, Salmonella Typhimurium T3SS-1-independent enteropathogenesis has also been demonstrated in murine and bovine infection models, and in chicken caecal and small-intestine explants (Coombes et al, 2005;Desin et al, 2009;Hapfelmeier et al, 2005).…”

The Different Strategies Used by Salmonella to Invade Host Cells

“…However, an increasing number of reports describe that different serotypes of Salmonella can induce host infection without a functional T3SS-1 (Penheiter et al, 1997;Jones et al, 2001;Karasova et al, 2010). This has been demonstrated with T3SS-1 mutants but also with clinical Salmonella strains (Hu et al, 2008). However, the majority of Salmonella invasion system studies have focused on the T3SS-1 and we have little information concerning the T3SS-1-independent entry processes.…”

“…In S. Enteritidis and S. Typhimurium, the T3SS-1 is not essential during systemic infection of one week-old chicken or BalB/c mouse nor during the intestinal colonization of rabbit ileal loops (Coombes et al, 2005;Jones et al, 2007;Karasova et al, 2010). Moreover, S. Senftenberg strains lacking SPI-1 are isolated from human clinical cases, suggesting that the T3SS-1 is dispensable by this serotype for the establishment of infection in humans (Hu et al, 2008).…”

Molecular insights into farm animal and zoonoticSalmonellainfections

“…For example, SipC messenger (m)RNA and protein levels vary between serovar Typhimurium and Choleraesuis strains in a manner that may partly explain differences in their ability to invade porcine intestinal mucosa and induce enteritis (Paulin et al 2007). Despite the role played by SPI-1 in intestinal colonization of mammals, it should be noted that strains exist that lack key functional components of T3SS-1 yet are associated with human disease (Hu et al 2008).…”