RT Journal Article
SR Electronic
T1 In vitro efficacy of acetohydroxyacid synthase inhibitors against clinical strains of Mycobacterium tuberculosis isolated from a hospital in Beijing, China.
JF Saudi Medical Journal
JO Saudi Med J
FD Prince Sultan Military Medical City
SP 1122
OP 1126
VO 32
IS 11
A1 Dong, Mei
A1 Wang, Di
A1 Jiang, Ying
A1 Zhao, Li
A1 Yang, Caie
A1 Wu, Chun
YR 2011
UL http://smj.org.sa/content/32/11/1122.abstract
AB OBJECTIVES: To assess the efficacy of acetohydroxyacid synthase (AHAS) inhibitors against Mycobacterium tuberculosis from China, including multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains.METHODS: In this study, the tube dilution method and Middlebrook 7H10 agar media were used to describe the in vitro efficacy of 3 AHAS inhibitors (sulfometuron methyl, monosulfuron, and monosulfuron-ester) against H37Rv and 26 clinical isolates, which include MDR-TB and XDR-TB strains, from the 309th Hospital of Chinese People's Liberation Army (PLA 309), Beijing, China. Cytotoxity of these compounds were then evaluated using the 3-[4,5-dimethylthiazol-2yl]-2,5-dipheny tetrazolium bromide assay with HBE cells. All the experiments were performed from January 2010 to November 2010 in the Department of Clinical Laboratory of the PLA 309 hospital.RESULTS: Sulfometuron methyl (minimum inhibitory concentration [MIC] range, 8-16 mg/L), monosulfuron-ester (MIC range, 8-16 mg/L), and monosulfuron (MIC range, 16-64 mg/L) showed significant activity against all Mycobacterium tuberculosis strains tested in this study in vitro, and they exhibited the same degree of activity against MDR and XDR isolates with that shown against the susceptible strains. All 3 compounds showed little cytotoxicity, with an IC50 against HBE cells greater than 300 mg/L.CONCLUSIONS: The results suggest that AHAS could serve as a target protein for the development of novel anti-TB therapeutics in China.