Scientific Publications by FDA Staff

Infect Immun 2006 Nov;74(11):6491-5

Protection elicited by two glutamine auxotrophs of Mycobacterium tuberculosis and in vivo growth phenotypes of the four unique glutamine synthetase mutants in a murine model.

Lee S, Jeon BY, Bardarov S, Chen M, Morris SL, Jacobs WR Jr

Jacobs WR (reprint author), Albert Einstein Coll Med, Howard Hughes Med Inst, 1300 Morris Pk Ave, Bronx, NY 10461 USA Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10461 USA Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA Univ Massachusetts, Dept Pathol, Worcester, MA 01605 USA

We generated four individual glutamine synthetase (GS) mutants (DeltaglnA1, DeltaglnA2, DeltaglnA3, and DeltaglnA4) and one triple mutant (DeltaglnA1EA2) of Mycobacterium tuberculosis to investigate the roles of GS enzymes. Subcutaneous immunization with the DeltaglnA1EA2 and DeltaglnA1 glutamine auxotrophic mutants conferred protection on C57BL/6 mice against an aerosol challenge with virulent M. tuberculosis, which was comparable to that provided by Mycobacterium bovis BCG vaccination.