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.

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.