Abstract

Over recent decades, Salmonella infection research has predominantly relied on murine infection models. However, in many cases the infection phenotypes of Salmonella pathovars in mice do not recapitulate human disease. For example, Salmonella Typhimurium ST313 is associated with enhanced invasive infection of immunocompromised people in Africa, but infection of mice and other animal models with ST313 have not consistently reproduced this invasive phenotype. The introduction of alternative infection models could help to improve the quality and reproducibility of pathogenesis research by facilitating larger-scale experiments. To investigate the virulence of S. Typhimurium ST313 in comparison with ST19, a combination of avian and insect disease models were used. We performed experimental infections in five lines of inbred and one line of outbred chickens, as well as in the alternative chick embryo and Galleria mellonella wax moth larvae models. This extensive set of experiments identified broadly similar patterns of disease caused by the African and global pathovariants of Salmonella Typhimurium in the chicken, the chicken embryo and insect models. A comprehensive analysis of all the chicken infection experiments revealed that the African ST313 isolate D23580 had a subtle phenotype of reduced levels of organ colonisation in inbred chickens, relative to ST19 strain 4/74. ST313 isolate D23580 also caused reduced mortality in chicken embryos and insect larvae, when compared with ST19 4/74. We conclude that these three infection models do not reproduce the characteristics of the systemic disease caused by S. Typhimurium ST313 in humans.

Highlights

  • Salmonella Typhimurium sequence type (ST) 313 is a novel pathovariant circulating in subSaharan Africa that causes invasive non-typhoidal Salmonella disease [1]

  • Salmonella Typhimurium sequence type 313 (ST313) is associated with systemic infection in human populations in sub-Saharan Africa, and contrasts with the related pathovariant sequence type 19 (ST19) which

  • The systemic pathology associated with ST313 infection in humans has been comprehensively documented in clinical and epidemiological studies, such pathology has been inconsistently reproduced in animal models of infection

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Summary

Introduction

Salmonella Typhimurium sequence type (ST) 313 is a novel pathovariant circulating in subSaharan Africa that causes invasive non-typhoidal Salmonella (iNTS) disease [1]. Typhimurium ST present throughout the rest of the world is ST19, which generally causes gastroenteritis. We reported the use of a comparative transcriptomic approach to identify genes that were differentially expressed between ST313 and ST19 in a variety of environmental conditions and during macrophage infection [2]. We used the chicken model to study the infection biology of ST313 and ST19 S. Typhimurium ST313 strains caused invasive disease in Lohmann brown chickens and caused a more invasive phenotype than ST19 strains at early stages of infection [3]. The research was limited by small sample sizes and the exclusive use of outbred chicken lines

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