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Updated: Jun 25, 2026
08:51
Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling
Published on: June 25, 2015
Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function
Suzanne E Osborne1, Don Walthers, Ana M Tomljenovic
1The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5.
Summary
Regulatory mutations significantly drive bacterial pathogen evolution by altering gene expression. A study on Salmonella typhimurium revealed how acquiring a new regulatory binding site enhanced fitness during host adaptation.
Area of Science:
- Microbial evolution
- Bacterial pathogenesis
- Genetics
Background:
- Horizontal gene transfer and protein-coding mutations are known drivers of pathogen evolution.
- The role of cis-regulatory mutations in generating phenotypic diversity and pathogen adaptation is less understood.
Purpose of the Study:
- To investigate the evolutionary significance of cis-regulatory mutations in bacterial adaptation.
- To demonstrate how rewiring regulatory elements can confer fitness advantages.
Main Methods:
- Mapping and rewiring of a cis-regulatory module controlling a gene essential for murine typhoid.
- Utilizing competitive infections in host animals to quantify fitness gains.
Main Results:
- Identified an evolved cis-regulatory module that enhances the function of the srfN gene in Salmonella typhimurium.
- Demonstrated that acquisition of a binding site for the SsrB regulator facilitated pathoadaptation.
- Quantified a significant fitness advantage conferred by this regulatory mutation during host infections.
Conclusions:
- Cis-regulatory mutations represent a critical mechanism for pathogen evolution.
- Altered transcriptional outputs resulting from regulatory mutations can be strongly selected for due to fitness benefits.
- This study highlights the adaptive potential of regulatory evolution in bacterial pathogens.
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