Single passage in mouse organs enhances the survival and spread of Salmonella enterica
Journal of the Royal Society Interface
Royal Society Publishing
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Dybowski, R., Restif, O., Goupy, A., Maskell, D., Mastroeni, P., & Grant, A. (2015). Single passage in mouse organs enhances the survival and spread of Salmonella enterica. Journal of the Royal Society Interface, 12 (20150702)https://doi.org/10.1098/rsif.2015.0702
Intravenous inoculation of Salmonella enterica serovar Typhimurium into mice is a prime experimental model of invasive salmonellosis. The use of wildtype isogenic tagged strains (WITS) in this system has revealed that bacteria undergo independent bottlenecks in the liver and spleen before establishing a systemic infection. We recently showed that those bacteria that survived the bottleneck exhibited enhanced growth when transferred to naive mice. In the present study, we set out to disentangle the components of this in vivo adaptation by inoculating mice with WITS grown either in vitro or in vivo. We developed an original method to estimate the replication and killing rates of bacteria from experimental data, which involved solving the probability-generating function of a non-homogeneous birth-death-immigration process. This revealed a low initial mortality in bacteria obtained from a donor animal. Next, an analysis of WITS distributions in the livers and spleens of recipient animals indicated that in vivo-passaged bacteria started spreading between organs earlier than in vitro-grown bacteria. These results further our understanding of the influence of passage in a host on the fitness and virulence of S. enterica and represent an advance in the power of investigation on the patterns and mechanisms of host-pathogen interactions.
This work was funded by a Medical Research Council (MRC) grant (G0801161) awarded to AJG, PM and DJM. RD was supported by BBSRC grant BB/I002189/1 awarded to PM. OR is supported by a University Research Fellowship from the Royal Society.
Royal Society (uf0762354)
Royal Society (uf120164)
External DOI: https://doi.org/10.1098/rsif.2015.0702
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252733
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Licence URL: http://creativecommons.org/licenses/by/4.0/