Abstract
Intravenous inoculation of Salmonella enterica serovar Typhimurium into mice is a prime experimental model of invasive salmonellosis. The use of wild-type 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 this 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 Salmonella enterica and represent an advance in the power of investigation on the patterns and mechanisms of host–pathogen interactions.
Highlights
Salmonella enterica is a facultative intracellular pathogen capable of causing a spectrum of diseases in humans and other animals
We showed that the initial control is mediated by the host’s production of reactive oxygen intermediates [4], it is not clear whether the subsequent shift in dynamics is due to bacterial adaptation
Typhimurium bacteria have been shown to form independent foci of infection in mouse organs [8], we modelled the dynamics of a single wild-type isogenic tagged strains (WITS) in a single organ governed by immigration from the bloodstream, replication and death
Summary
Salmonella enterica is a facultative intracellular pathogen capable of causing a spectrum of diseases in humans and other animals. Variations in microbial loads in the organs of animals can be quantified post-mortem by plating homogenized tissues on solid culture medium, and counting the numbers of colony-forming units (CFUs) after incubation. While this method provides accurate estimates of the net growth rates of bacterial populations, it bears no information about the respective rates of the underlying processes of bacterial replication, death and migration. For this purpose, various experimental methods for tracking subpopulations of bacteria have been developed [3].
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