title: Single passage in mouse organs enhances the survival and spread of Salmonella enterica.
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.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Dybowski
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
authors.forename: Olivier
authors.initials: O
authors.lastname: Restif
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK ENSTA-ParisTech, 828 Boulevard des Maréchaux, Palaiseau 91120, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Goupy
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Maskell
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
authors.forename: Piero
authors.initials: P
authors.lastname: Mastroeni
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK ajg60@cam.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Grant
mesh_terms: D000818:Animals; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D012480:Salmonella Infections / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D013154:Spleen / Q000378:metabolism / Q000382:microbiology
keywords: Bayesian; bacteria; infection; population dynamics