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Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ.

Gal-Mor O, Boyle EC, Grassl GA - Front Microbiol (2014)

Bottom Line: Despite their genetic similarity, these two groups elicit very different diseases and distinct immune responses in humans.Comparative analyses of the genomes of multiple Salmonella serovars have begun to explain the basis of the variation in disease manifestations.Understanding the genetic and molecular mechanisms responsible for differences in disease outcome will augment our understanding of Salmonella pathogenesis, host immunity, and the molecular basis of host specificity.

View Article: PubMed Central - PubMed

Affiliation: The Infectious Diseases Research Laboratory, Sheba Medical Center Tel-Hashomer, Israel.

ABSTRACT
Human infections by the bacterial pathogen Salmonella enterica represent major disease burdens worldwide. This highly ubiquitous species consists of more than 2600 different serovars that can be divided into typhoidal and non-typhoidal Salmonella (NTS) serovars. Despite their genetic similarity, these two groups elicit very different diseases and distinct immune responses in humans. Comparative analyses of the genomes of multiple Salmonella serovars have begun to explain the basis of the variation in disease manifestations. Recent advances in modeling both enteric fever and intestinal gastroenteritis in mice will facilitate investigation into both the bacterial- and host-mediated mechanisms involved in salmonelloses. Understanding the genetic and molecular mechanisms responsible for differences in disease outcome will augment our understanding of Salmonella pathogenesis, host immunity, and the molecular basis of host specificity. This review outlines the differences in epidemiology, clinical manifestations, and the human immune response to typhoidal and NTS infections and summarizes the current thinking on why these differences might exist.

No MeSH data available.


Related in: MedlinePlus

Molecular bases for differences between typhoidal and NTS serovars. (A) Typhoidal serovars possess several inactive/degraded genes compared to NTS serovars such as genes for chemotaxis, adhesion, and anaerobic metabolism. (B) Both typhoidal and NTS serovars possess unique virulence factors. For example, some S. Typhi strains express Vi capsule that reduces TLR-dependent IL-8 production in the intestinal mucosa. However, while the Vi capsule plays a role in typhoid fever manifestation, it is not necessary as it is absent from other typhoidal serovars and Vi-negative mutants of S. Typhi are still able to cause a typhoid-like illness in humans. (C) In contrast to typhoidal serovars, NTS cause severe intestinal inflammation. NTS serovars have evolved to utilize inflammation-derived metabolites (e.g., nitrate and tetrathionate), thereby enhancing their growth in the inflamed intestine. Typhoidal serovars have lost the ability to benefit from inflammation-derived metabolites and disseminate to systemic sites to a much greater extent.
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Figure 1: Molecular bases for differences between typhoidal and NTS serovars. (A) Typhoidal serovars possess several inactive/degraded genes compared to NTS serovars such as genes for chemotaxis, adhesion, and anaerobic metabolism. (B) Both typhoidal and NTS serovars possess unique virulence factors. For example, some S. Typhi strains express Vi capsule that reduces TLR-dependent IL-8 production in the intestinal mucosa. However, while the Vi capsule plays a role in typhoid fever manifestation, it is not necessary as it is absent from other typhoidal serovars and Vi-negative mutants of S. Typhi are still able to cause a typhoid-like illness in humans. (C) In contrast to typhoidal serovars, NTS cause severe intestinal inflammation. NTS serovars have evolved to utilize inflammation-derived metabolites (e.g., nitrate and tetrathionate), thereby enhancing their growth in the inflamed intestine. Typhoidal serovars have lost the ability to benefit from inflammation-derived metabolites and disseminate to systemic sites to a much greater extent.

Mentions: In vitro tissue culture studies suggest that S. Typhi induces restrained inflammatory responses that do not trigger a pro-inflammatory response via TLR5. Similarly, polarized human colonic epithelial (T84) cells infected with S. Typhi induce significantly lower levels of the neutrophil chemoattractant IL-8 compared to S. Typhimurium infection (Raffatellu et al., 2005). Raffatellu et al. (2008b) have therefore postulated that S. Typhi expresses unique virulence factors that allow this pathogen to overcome the innate immune response in the intestinal mucosa resulting in the absence of neutrophil infiltration and inflammatory diarrhea. One of the current hypotheses in the field suggests that the polysaccharide capsular antigen Vi in S. Typhi enables this pathogen to resist phagocytosis and complement killing (Robbins and Robbins, 1984) and masks access to pattern recognition molecules, resulting in less IL-8 production (Raffatellu et al., 2005), limited neutrophil influx, and thereby reduced small bowel inflammation (Sharma and Qadri, 2004; Wilson et al., 2008). The role of the Vi antigen regulator TviA, and its putative contribution to S. Typhi’s ability to evade the immune system have been recently reviewed (Wangdi et al., 2012). Nevertheless, since the Vi capsule is largely restricted to serovar Typhi and is absent from serovars Paratyphi A and Sendai, it cannot explain why the clinical manifestations of these other typhoidal serovars differ from that of NTS. Furthermore, the fact that Vi-negative mutants of S. Typhi are still able to cause a typhoid-like illness in human volunteers (Zhang et al., 2008), suggests that additional mechanisms are involved (Figure 1).


Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ.

Gal-Mor O, Boyle EC, Grassl GA - Front Microbiol (2014)

Molecular bases for differences between typhoidal and NTS serovars. (A) Typhoidal serovars possess several inactive/degraded genes compared to NTS serovars such as genes for chemotaxis, adhesion, and anaerobic metabolism. (B) Both typhoidal and NTS serovars possess unique virulence factors. For example, some S. Typhi strains express Vi capsule that reduces TLR-dependent IL-8 production in the intestinal mucosa. However, while the Vi capsule plays a role in typhoid fever manifestation, it is not necessary as it is absent from other typhoidal serovars and Vi-negative mutants of S. Typhi are still able to cause a typhoid-like illness in humans. (C) In contrast to typhoidal serovars, NTS cause severe intestinal inflammation. NTS serovars have evolved to utilize inflammation-derived metabolites (e.g., nitrate and tetrathionate), thereby enhancing their growth in the inflamed intestine. Typhoidal serovars have lost the ability to benefit from inflammation-derived metabolites and disseminate to systemic sites to a much greater extent.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120697&req=5

Figure 1: Molecular bases for differences between typhoidal and NTS serovars. (A) Typhoidal serovars possess several inactive/degraded genes compared to NTS serovars such as genes for chemotaxis, adhesion, and anaerobic metabolism. (B) Both typhoidal and NTS serovars possess unique virulence factors. For example, some S. Typhi strains express Vi capsule that reduces TLR-dependent IL-8 production in the intestinal mucosa. However, while the Vi capsule plays a role in typhoid fever manifestation, it is not necessary as it is absent from other typhoidal serovars and Vi-negative mutants of S. Typhi are still able to cause a typhoid-like illness in humans. (C) In contrast to typhoidal serovars, NTS cause severe intestinal inflammation. NTS serovars have evolved to utilize inflammation-derived metabolites (e.g., nitrate and tetrathionate), thereby enhancing their growth in the inflamed intestine. Typhoidal serovars have lost the ability to benefit from inflammation-derived metabolites and disseminate to systemic sites to a much greater extent.
Mentions: In vitro tissue culture studies suggest that S. Typhi induces restrained inflammatory responses that do not trigger a pro-inflammatory response via TLR5. Similarly, polarized human colonic epithelial (T84) cells infected with S. Typhi induce significantly lower levels of the neutrophil chemoattractant IL-8 compared to S. Typhimurium infection (Raffatellu et al., 2005). Raffatellu et al. (2008b) have therefore postulated that S. Typhi expresses unique virulence factors that allow this pathogen to overcome the innate immune response in the intestinal mucosa resulting in the absence of neutrophil infiltration and inflammatory diarrhea. One of the current hypotheses in the field suggests that the polysaccharide capsular antigen Vi in S. Typhi enables this pathogen to resist phagocytosis and complement killing (Robbins and Robbins, 1984) and masks access to pattern recognition molecules, resulting in less IL-8 production (Raffatellu et al., 2005), limited neutrophil influx, and thereby reduced small bowel inflammation (Sharma and Qadri, 2004; Wilson et al., 2008). The role of the Vi antigen regulator TviA, and its putative contribution to S. Typhi’s ability to evade the immune system have been recently reviewed (Wangdi et al., 2012). Nevertheless, since the Vi capsule is largely restricted to serovar Typhi and is absent from serovars Paratyphi A and Sendai, it cannot explain why the clinical manifestations of these other typhoidal serovars differ from that of NTS. Furthermore, the fact that Vi-negative mutants of S. Typhi are still able to cause a typhoid-like illness in human volunteers (Zhang et al., 2008), suggests that additional mechanisms are involved (Figure 1).

Bottom Line: Despite their genetic similarity, these two groups elicit very different diseases and distinct immune responses in humans.Comparative analyses of the genomes of multiple Salmonella serovars have begun to explain the basis of the variation in disease manifestations.Understanding the genetic and molecular mechanisms responsible for differences in disease outcome will augment our understanding of Salmonella pathogenesis, host immunity, and the molecular basis of host specificity.

View Article: PubMed Central - PubMed

Affiliation: The Infectious Diseases Research Laboratory, Sheba Medical Center Tel-Hashomer, Israel.

ABSTRACT
Human infections by the bacterial pathogen Salmonella enterica represent major disease burdens worldwide. This highly ubiquitous species consists of more than 2600 different serovars that can be divided into typhoidal and non-typhoidal Salmonella (NTS) serovars. Despite their genetic similarity, these two groups elicit very different diseases and distinct immune responses in humans. Comparative analyses of the genomes of multiple Salmonella serovars have begun to explain the basis of the variation in disease manifestations. Recent advances in modeling both enteric fever and intestinal gastroenteritis in mice will facilitate investigation into both the bacterial- and host-mediated mechanisms involved in salmonelloses. Understanding the genetic and molecular mechanisms responsible for differences in disease outcome will augment our understanding of Salmonella pathogenesis, host immunity, and the molecular basis of host specificity. This review outlines the differences in epidemiology, clinical manifestations, and the human immune response to typhoidal and NTS infections and summarizes the current thinking on why these differences might exist.

No MeSH data available.


Related in: MedlinePlus