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Published on: April 9, 2018
MarA, SoxS and Rob function as virulence factors in an Escherichia coli murine model of ascending pyelonephritis
Paul Casaz1, Lynne K Garrity-Ryan1, David McKenney1
1Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA.
Abstract:
MarA, SoxS and Rob are transcription factors belonging to the AraC family. While these proteins have been associated historically with control of multiple antibiotic resistance, and tolerance to oxidative stress agents and organic solvents, only a paucity of experimental data support a role in regulating virulence. Clinical Escherichia coli isolates, and isogenic strains lacking marA, soxS and rob, were studied in a murine model of ascending pyelonephritis, which is a clinically relevant model of urinary tract infection. Organisms lacking all three transcription factors (triple knockouts) were significantly less virulent than parental strains, and complementation studies demonstrated that the addition of marA, soxS and rob individually restored wild-type virulence in the triple-knockout strain. Deletion of soxS or rob alone was more detrimental than the removal of marA. Thus, all three proteins contribute to virulence in vivo.
Insights
MarA, SoxS, and Rob transcription factors are crucial for Escherichia coli virulence in urinary tract infections. Deleting these factors significantly reduces bacterial infection severity in a mouse model.
Area of Science:
- Microbiology and Molecular Biology
- Bacterial Pathogenesis and Virulence Factors
- Genetics and Gene Regulation
Background:
- MarA, SoxS, and Rob are AraC family transcription factors historically linked to antibiotic resistance and stress tolerance.
- Limited experimental data exist regarding their role in bacterial virulence regulation.
Purpose of the Study:
- To investigate the role of MarA, SoxS, and Rob transcription factors in the virulence of *Escherichia coli*.
- To assess the contribution of these factors in a clinically relevant model of urinary tract infection.
Main Methods:
- Utilized a murine model of ascending pyelonephritis to study *E. coli* virulence.
- Compared virulence of clinical isolates with isogenic strains lacking individual or all three transcription factors (marA, soxS, rob).
- Performed complementation studies to confirm the role of each transcription factor.
Main Results:
- Triple knockout strains lacking MarA, SoxS, and Rob were significantly less virulent than parental strains.
- Complementation with individual factors restored wild-type virulence in the triple knockout.
- Deletion of soxS or rob alone had a more detrimental effect on virulence than marA deletion.
Conclusions:
- MarA, SoxS, and Rob transcription factors collectively contribute to *E. coli* virulence in vivo.
- These factors play a significant role in the pathogenesis of urinary tract infections.
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