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

Casaz P, Garrity-Ryan LK, McKenney D, Jackson C, Levy SB, Tanaka SK, Alekshun MN

Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA.

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.

Published 12 December 2006 in Microbiology, 152: 3643-50.
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