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Microbiology 152 (2006), 3643-3650; DOI  10.1099/mic.0.2006/000604-0
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Microbiology 152 (2006), 3643-3650; DOI  10.1099/mic.0.2006/000604-0
© 2006 Society for General Microbiology

MarA, SoxS and Rob function as virulence factors in an Escherichia coli murine model of ascending pyelonephritis

Paul Casaz1,{dagger}, Lynne K. Garrity-Ryan1, David McKenney1, Caroline Jackson1, Stuart B. Levy1,2, S. Ken Tanaka1 and Michael N. Alekshun1,{ddagger}

1 Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA
2 Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA

Correspondence
Stuart B. Levy
stuart.levy{at}tufts.edu

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.

Abbreviations: TTSS, type III secretion system; UPEC, uropathogenic E. coli; UTI, urinary tract infection; VUR, vesicoureteral reflux

{dagger}Present address: Massachusetts Biologics Laboratories, 305 South Street, Jamaica Plain, MA 02130, USA.

{ddagger}Present address: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0530, USA.






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Copyright © 2006 Society for General Microbiology.