Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function

Suzanne E. Osborne, Don Walthers, Ana M. Tomljenovic, David T. Mulder, Uma Silphaduang, Nancy Duong, Michael J. Lowden, Mark E. Wickham, Ross F. Waller, Linda J. Kenney, Brian K. Coombes

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones.

Original languageEnglish (US)
Pages (from-to)3982-3987
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - Mar 10 2009
Externally publishedYes


  • Bacterial pathogenesis
  • Evo-devo
  • Pathoadaptation
  • Regulatory evolution
  • cis-regulatory mutation

ASJC Scopus subject areas

  • General


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