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Mycobacterium tuberculosis acg Gene Is Required for Growth and Virulence In Vivo.

Hu, Y; Coates, AR (2011) Mycobacterium tuberculosis acg Gene Is Required for Growth and Virulence In Vivo. PLOS ONE, 6 (6). e20958. ISSN 1932-6203
SGUL Authors: Coates, Anthony Robert Milnes Hu, Yanmin

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Mycobacterium tuberculosis dosRS two-component regulatory system controls transcription of approximately 50 genes including hspX, acg and Rv2030c, in response to hypoxia and nitric oxide conditions and within macrophages and mice. The hspX lies between acg and Rv2030c. However, the functions of the dosR regulated genes in vitro and in vivo are largely unknown. Previously, we demonstrated that deletion of hspX gene produced a mutant which grew faster in macrophages and in mice. In this study, we attempted to determine the functions of acg and Rv2030c by gene inactivation. We demonstrate that Rv2030c is dispensable for virulence and growth. However, deletion of acg produced a mutant which is attenuated in both resting and activated macrophages and in acute and persistent murine infection models. Surprisingly, deletion of acg did not compromise the viability of the mutant to nitrosative and oxidative stresses in vitro and in vivo. In addition, when the WT and the acg mutants were treated with antibiotics such as the prodrugs nitrofurantoin and nitrofuran, the acg mutant became more sensitive than the WT strain to these drugs. This suggests that Acg may not function as a nitroreductase. These data indicate that acg encodes an essential virulence factor for M. tuberculosis and enables it to grow and survive in macrophages and in mouse organs.

Item Type: Article
Additional Information: ©2011 Hu Coates. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Animals, Female, Gene Deletion, Genes, Bacterial, Inflammation, Macrophages, Mice, Mice, Inbred BALB C, Mycobacterium tuberculosis, Nitroreductases, Stress, Physiological, Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, ALPHA-CRYSTALLIN, HYPOXIC RESPONSE, OXIDATIVE STRESS, STATIONARY-PHASE, CARBON-MONOXIDE, BOVIS BCG, HSPX GENE, EXPRESSION, TRANSCRIPTION
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: PLOS ONE
ISSN: 1932-6203
8 June 2011Published
PubMed ID: 21687631
Web of Science ID: 21687631
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