Typhoid and paratyphoid fever are indistinguishable in their symptoms, suggesting that typhoidal Salmonella serovars possess similar virulence strategies. However, the identity of shared virulence strategies that set typhoidal Salmonella serovars apart from non-typhoidal Salmonella serovars, such as S. enterica serovar Typhimurium, remain understudied. Experiments proposed in this application are aimed at addressing this important gap in knowledge. Our long-range goal is to elucidate the molecular mechanisms by which typhoidal Salmonella serotypes manipulate host responses during infection. The objectives of this application are to study the contribution of genome decay in typhoidal Salmonella serovars, which includes gene deletion or disruption (pseudogene formation), to their interaction with the human host. Our central hypothesis is that genome decay in typhoidal Salmonella serovars is a key driver of immune evasion. To test our hypothesis, we will determine whether pseudogen formation enables S. Paratyphi A to evade complement activation (specific aim 1), determine how reduced epithelial invasion caused by genome decay moderates gut inflammation (specific aim 2) and determine how pseudogene formation enhances Peyer's patch colonization (specific aim 3). Our analysis of virulence mechanisms shared among typhoidal Salmonella serovars will be useful, and necessary, to understand how the interplay between pathogen and the innate immune system gives rise to responses that distinguish typhoid/paratyphoid fever from gastroenteritis, thereby ushering in a significant conceptual advance.
Typhoidal Salmonella serovars cause an estimated 27 million cases of typhoid/paratyphoid fever each year. Due to the absence of convenient animals models to study these pathogens, our understanding of typhoid/paratyphoid fever pathogenesis is still incomplete. In this application, we will elucidate how typhoidal Salmonella serovars evade our immune system, which will provide important new insights into the pathogenesis of typhoid and paratyphoid fever.
| Litvak, Yael; Byndloss, Mariana X; Bäumler, Andreas J (2018) Colonocyte metabolism shapes the gut microbiota. Science 362: |
| Hiyoshi, Hirotaka; Wangdi, Tamding; Lock, Gabriel et al. (2018) Mechanisms to Evade the Phagocyte Respiratory Burst Arose by Convergent Evolution in Typhoidal Salmonella Serovars. Cell Rep 22:1787-1797 |
| Lopez, Christopher A; Miller, Brittany M; Rivera-Chávez, Fabian et al. (2016) Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration. Science 353:1249-53 |
| Keestra-Gounder, A Marijke; Byndloss, Mariana X; Seyffert, Núbia et al. (2016) NOD1 and NOD2 signalling links ER stress with inflammation. Nature 532:394-7 |
| Vázquez-Torres, Andrés; Bäumler, Andreas J (2016) Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens. Curr Opin Microbiol 29:1-8 |
| Song, Jeongmin; Wilhelm, Cara L; Wangdi, Tamding et al. (2016) Absence of TLR11 in Mice Does Not Confer Susceptibility to Salmonella Typhi. Cell 164:827-8 |
| Bäumler, Andreas J; Sperandio, Vanessa (2016) Interactions between the microbiota and pathogenic bacteria in the gut. Nature 535:85-93 |
| Rivera-Chávez, Fabian; Zhang, Lillian F; Faber, Franziska et al. (2016) Depletion of Butyrate-Producing Clostridia from the Gut Microbiota Drives an Aerobic Luminal Expansion of Salmonella. Cell Host Microbe 19:443-54 |
| Winter, Sebastian E; Winter, Maria G; Atluri, Vidya et al. (2015) The flagellar regulator TviA reduces pyroptosis by Salmonella enterica serovar Typhi. Infect Immun 83:1546-55 |
| Keestra-Gounder, A Marijke; Tsolis, Renée M; Bäumler, Andreas J (2015) Now you see me, now you don't: the interaction of Salmonella with innate immune receptors. Nat Rev Microbiol 13:206-16 |
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