Construction and Phenotypic Characterization of an Auxotrophic Mutant of Mycobacterium Tuberculosis Defective in L-arginine Biosynthesis

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2002 May 16

PMID 12011001

Citations 36

Authors

Bhavna G Gordhan

Debbie A Smith

Heidi Alderton

Ruth A McAdam

Gregory J Bancroft

Valerie Mizrahi

Affiliations

Soon will be listed here.

Abstract

A mutant of Mycobacterium tuberculosis defective in the metabolism of L-arginine was constructed by allelic exchange mutagenesis. The argF mutant strain required exogenous L-arginine for growth in vitro, and in the presence of 0.96 mM L-arginine, it achieved a growth rate and cell density in stationary phase comparable to those of the wild type. The mutant strain was also able to grow in the presence of high concentrations of argininosuccinate, but its auxotrophic phenotype could not be rescued by L-citrulline, suggesting that the DeltaargF::hyg mutation exerted a polar effect on the downstream argG gene but not on argH. The mutant strain displayed reduced virulence in immunodeficient SCID mice and was highly attenuated in immunocompetent DBA/2 mice, suggesting that L-arginine availability is restricted in vivo.

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