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Comparative evaluation of Salmonella Typhimurium vaccines derived from UK-1 and 14028S: Importance of inherent virulence.

ABSTRACT: The initial virulence and invasiveness of a bacterial strain may play an important role in leading to a maximally efficacious attenuated live vaccine. Here we show that ?9909, derived from Salmonella Typhimurium UK-1 ?3761 (the most virulent S. Typhimurium strain known to us), is effective in protecting mice against lethal UK-1 and 14028S (less virulent S. Typhimurium strain) challenge. As opposed to this, 14028S-derived vaccine ?12359 induces suboptimal levels of protection, with survival percentages that are significantly lower when challenged with lethal UK-1 challenge doses. T-cell assays have revealed that significantly greater levels of Th1 cytokines IFN-? and TNF-? were secreted by stimulated T-lymphocytes obtained from UK-1(?aroA) immunized mice than those from mice immunized with 14028S(?aroA). In addition, UK-1(?aroA) showed markedly higher colonizing ability in the spleen, liver, and cecum when compared to 14028S(?aroA). Enumeration of bacteria in fecal pellets has also revealed that UK-1(?aroA) can persist in the host for over 10 days whereas 14028S(?aroA) titers dropped significantly by day 10. Moreover, co-infection of parent strains UK-1 and 14028S resulted in considerably greater recovery of the former in multiple mucosal and gut associated lymphatic tissues. Mice immunized with UK-1(?aroA) were also able to clear UK-1 infection remarkably more efficiently from the target organs than 14028S(?aroA). Together, these results provide ample evidence to support the hypothesis that attenuated derivatives of parent strains with higher initial virulence make better vaccines.

SUBMITTER: Sanapala S

PROVIDER: S-EPMC6130210 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Comparative evaluation of Salmonella Typhimurium vaccines derived from UK-1 and 14028S: Importance of inherent virulence.

Sanapala Shilpa S Mosca Leandra L Wang Shifeng S Curtiss Roy R

PloS one 20180907 9

The initial virulence and invasiveness of a bacterial strain may play an important role in leading to a maximally efficacious attenuated live vaccine. Here we show that χ9909, derived from Salmonella Typhimurium UK-1 χ3761 (the most virulent S. Typhimurium strain known to us), is effective in protecting mice against lethal UK-1 and 14028S (less virulent S. Typhimurium strain) challenge. As opposed to this, 14028S-derived vaccine χ12359 induces suboptimal levels of protection, with survival perce ...[more]

PMID: 30192849

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Project description:Contamination of edible produce leaves with human bacterial pathogens has been associated with serious disease outbreaks and has become a major public health concern affecting all aspects of the market, from farmers to consumers. While pathogen populations residing on the surface of ready-to-eat produce can be potentially removed through thorough washing, there is no disinfection technology available that effectively eliminates internal bacterial populations. By screening 303 multi-gene deletion (MGD) mutants of Salmonella enterica serovar Typhimurium (STm) 14028s, we were able to identify ten genomic regions that play a role in opening the stomatal pore of lettuce leaves. The major metabolic functions of the deleted regions are associated with sensing the environment, bacterium movement, transport through the bacterial membrane, and biosynthesis of surface appendages. Interestingly, at 21 days post inoculation, seven of these mutants showed increased population titers inside the leaf, two mutants showed similar titers as the wild type bacterium, whereas one mutant with a large deletion that includes the Salmonella pathogenicity island 2 (SPI-2) showed significantly impaired persistence in the leaf apoplast. These findings suggest that not all the genomic regions required for initiation of leaf colonization (i.e., epiphytic behavior and tissue penetration) are essential for continuing bacterial survival as an endophyte. We also observed that mutants lacking either SPI-1 (Mut3) or SPI-2 (Mut9) induce callose deposition levels comparable to those of the wild type STm 14028s; therefore, these islands do not seem to affect this lettuce defense mechanism. However, the growth of Mut9, but not Mut3, was significantly impaired in the leaf apoplastic wash fluid (AWF) suggesting that the STm persistence in the apoplast may be linked to nutrient acquisition capabilities or overall bacterial fitness in this niche, which are dependent on the gene(s) deleted in the Mut9 strain. The genetic basis of STm colonization of leaves investigated in this study provides a foundation from which to develop mitigation tactics to enhance food safety.

Dataset Information

Comparative evaluation of Salmonella Typhimurium vaccines derived from UK-1 and 14028S: Importance of inherent virulence.

Publications

Comparative evaluation of Salmonella Typhimurium vaccines derived from UK-1 and 14028S: Importance of inherent virulence.

Similar Datasets

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