Affiliation:
1. Department of Chemistry and Biochemistry
2. Department of Pathology, University of California, San Diego, La Jolla, California 92093
Abstract
ABSTRACT
Mycothiol (MSH) is the major low-molecular-mass thiol in mycobacteria and is associated with the protection of
Mycobacterium tuberculosis
from toxic oxidants and antibiotics. The biosynthesis of MSH is a multistep process, with the enzymatic reaction designated MshC being the ligase step in MSH production. A targeted disruption of the native
mshC
gene in
M
.
tuberculosis
Erdman produced no viable clones possessing either a disrupted
mshC
gene or reduced levels of MSH. However, when a second copy of the
mshC
gene was incorporated into the chromosome prior to the targeted disruption, multiple clones having the native gene disrupted and the second copy of
mshC
intact were obtained. These clones produced normal levels of MSH. These results demonstrate that the
mshC
gene and, more generally, the production of MSH are essential for the growth of
M. tuberculosis
Erdman under laboratory conditions.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Reference16 articles.
1. Bardarov, S., S. Bardarov, Jr., M. S. Pavelka, Jr., V. Sambandamurthy, M. Larsen, J. Tufariello, J. Chan, G. Hatfull, and W. R. Jacobs, Jr. 2002. Specialized transduction: an efficient method for generating marked and unmarked targeted gene disruptions in Mycobacterium tuberculosis, M. bovis BCG and M. smegmatis.Microbiology148:3007-3017.
2. Bardarov, S., J. Kriakov, C. Carriere, S. Yu, C. Vaamonde, R. A. McAdam, B. R. Bloom, G. F. Hatfull, and W. R. Jacobs, Jr. 1997. Conditionally replicating mycobacteriophages: a system for transposon delivery to Mycobacterium tuberculosis.Proc. Natl. Acad. Sci. USA94:10961-10966.
3. Buchmeier, N., A. Blanc-Potard, S. Ehrt, D. Piddington, L. Riley, and E. A. Groisman. 2000. A parallel intraphagosomal survival strategy shared by Mycobacterium tuberculosis and Salmonella enterica.Mol. Microbiol.35:1375-1382.
4. Buchmeier, N. A., G. L. Newton, T. Koledin, and R. C. Fahey. 2003. Association of mycothiol with protection of Mycobacterium tuberculosis from toxic oxidants and antibiotics. Mol. Microbiol.47:1723-1732.
5. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence