Repression of Flagella Is a Common Trait in Field Isolates of Salmonella enterica Serovar Dublin and Is Associated with Invasive Human Infections

Abstract

eThe nontyphoidal Salmonella enterica serovar Dublin is adapted to cattle but infrequently infects humans, very often resulting in invasive infections with high levels of morbidity and mortality. A Salmonella-induced intestinal acute inflammatory response is postulated as a mechanism to prevent bacterial dissemination to systemic sites. In S. enterica serovar Typhimurium, flagella contribute to this response by providing motility and FliC-mediated activation of pattern recognition receptors. In this study, we found 4 Salmonella enterica isolates, with the antigenic formula 9,12:؊:؊, that, based on fliC sequence and multilocus sequence type (MLST) analyses, are aflagellate S. Dublin isolates. Interestingly, all were obtained from human bloodstream infections. Thus, we investigated the potential role of flagella in the unusual invasiveness exhibited by S. Dublin in humans by analyzing flagellation and proinflammatory properties of a collection of 10 S. Dublin human clinical isolates. We found that 4 of 7 blood isolates were aflagellate due to significantly reduced levels of fliC expression, whereas all 3 isolates from other sources were flagellated. Lack of flagella correlated with a reduced ability of triggering interleukin-8 (IL-8) and CCL20 chemokine expression in human intestinal Caco-2 cells and with reduced early inflammation in the ceca of streptomycin-pretreated C57/BL6 mice. These results indicate that flagella contribute to the host intestinal inflammatory response to Salmonella serovar Dublin and suggest that their absence may contribute to its systemic dissemination through dampening of the gut immune response. Analysis of FliC production in a collection of cattle isolates indicated that the aflagellate phenotype is widely distributed in field isolates of S. Dublin.

Genetic diversity, anti‐microbial resistance, plasmid profile and frequency of the Vi antigen in Salmonella Dublin strains isolated in Brazil

“…Dublin is highly invasive in comparison to other non‐typhi serovars, with invasion indexes >40%, while the indexes for other serovars, like Enteritidis and Typhimurium, rarely exceeds 5%. The bacterial factors responsible for this invasive characteristic in humans are still unknown (Betancor et al., ; Nielsen, ; Uzzau et al., ; Yim et al., ).…”

“…The only serovars expressing this polysaccharide are Typhi and Paratyphi, both causing systemic infection in humans. Furthermore, some strains of this serovar isolated from the human bloodstream have been shown to be non‐flagellated, which can help to explain the success of this invasive disease in humans, once flagella production triggers the immune response in humans (Yim et al., ). Another characteristic that enhances S .…”

Urocystitis and Ureteritis in Holstein Calves with Septicaemia Caused by Salmonella enterica Serotype Dublin

“…Cattle are a host-adapted species for S. Dublin and are considered a good experimental model for non-typhoidal salmonellosis in man (Costa et al, 2012). Salmonella Dublin also causes invasive infections in man (Yim et al, 2014).…”

Non-typhoidal Salmonella Typhimurium ST313 isolates that cause bacteremia in humans stimulate less inflammasome activation than ST19 isolates associated with gastroenteritis

“…, 2013; Yim et al. , 2014). Similarly, the S. Typhimurium DT2 clade, which is restricted to feral pigeons and causes a typhoid-like disease in these animals, downregulates the expression of flagellar and SPI-1 genes at 42°C, which is the approximate body temperature of pigeons (Kingsley et al.…”