Intracellular demography and the dynamics of Salmonella enterica infections

Sam P. Brown, Stephen J. Cornell, Mark Sheppard, Andrew J. Grant, Duncan J. Maskell, Bryan T. Grenfell, Pietro Mastroeni

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

An understanding of within-host dynamics of pathogen interactions with eukaryotic cells can shape the development of effective preventive measures and drug regimes. Such investigations have been hampered by the difficulty of identifying and observing directly, within live tissues, the multiple key variables that underlay infection processes. Fluorescence microscopy data on intracellular distributions of Salmonella enterica serovar Typhimurium (S. Typhimurium) show that, while the number of infected cells increases with time, the distribution of bacteria between cells is stationary (though highly skewed). Here, we report a simple model framework for the intensity of intracellular infection that links the quasi-stationary distribution of bacteria to bacterial and cellular demography. This enables us to reject the hypothesis that the skewed distribution is generated by intrinsic cellular heterogeneities, and to derive specific predictions on the within-cell dynamics of Salmonella division and host-cell lysis. For within-cell pathogens in general, we show that within-cell dynamics have implications across pathogen dynamics, evolution, and control, and we develop novel generic guidelines for the design of antibacterial combination therapies and the management of antibiotic resistance. Copyright:

Original languageEnglish (US)
Pages (from-to)2091-2098
Number of pages8
JournalPLoS biology
Volume4
Issue number11
DOIs
StatePublished - Nov 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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    Brown, S. P., Cornell, S. J., Sheppard, M., Grant, A. J., Maskell, D. J., Grenfell, B. T., & Mastroeni, P. (2006). Intracellular demography and the dynamics of Salmonella enterica infections. PLoS biology, 4(11), 2091-2098. https://doi.org/10.1371/journal.pbio.0040349