Mycobacterium tuberculosis Arylamine N-Acetyltransferase Acetylates and Thus Inactivates para-Aminosalicylic Acid.
Mycobacterium tuberculosis arylamine N-acetyltransferase (TBNAT) is able to acetylate para-aminosalicylic acid (PAS) both in vitro and in vivo as determined by high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS) techniques. The antituberculosis activity of the acetylated PAS is significantly reduced. As a result, overexpression of TBNAT in M. tuberculosis results in PAS resistance, as determined by MIC tests and drug exposure experiments. Taken together, our results suggest that TBNAT from M. tuberculosis is able to inactivate PAS by acetylating the compound.
Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.|School of Stomatology and Medicine, Foshan University, Foshan, China.
Xude
X
Wang
Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Shanshan
S
Yang
Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Jing
J
Gu
Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China dengjy@wh.iov.cn.
Jiaoyu
J
Deng
D000107:Acetylation; D010131:Aminosalicylic Acid / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D000995:Antitubercular Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015870:Gene Expression; D008658:Inactivation, Metabolic; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D021241:Spectrometry, Mass, Electrospray Ionization
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D010131:Aminosalicylic Acid; D001191:Arylamine N-Acetyltransferase
Toxicology. 2008 Dec 30;254(3):170-83
18852012
Protein J. 2009 Aug;28(6):281-93
19636684
J Biol Chem. 1971 May 25;246(10):3250-8
5103348
DNA Res. 2005;12(5):291-9
16769691
Pharmacol Ther. 1989;42(2):157-234
2664821
Lancet. 1946 Jan 5;1(6384):15
21008766
Biochem J. 2005 Jan 15;385(Pt 2):605-12
15447630
J Biol Chem. 1992 Apr 25;267(12):8429-36
1569093
J Biol Chem. 1990 Mar 15;265(8):4630-4
1968463
Biochemistry. 2008 Oct 7;47(40):10781-9
18795795
Curr Microbiol. 1998 Jun;36(6):353-60
9608747
Cancer Epidemiol Biomarkers Prev. 2000 Jan;9(1):29-42
10667461
Br J Pharmacol. 2014 Jun;171(11):2705-25
24467436
Expert Opin Drug Metab Toxicol. 2009 Apr;5(4):353-66
19379125
Mol Microbiol. 2001 Oct;42(2):309-17
11703656
Br Med J. 1960 Aug 13;2(5197):485-91
13820968
Protein Sci. 2005 Mar;14(3):775-82
15722451
Science. 2013 Jan 4;339(6115):88-91
23118010
Biochem J. 1994 Feb 1;297 ( Pt 3):441-5
8110178
BMC Biochem. 2007 Mar 20;8:3
17374145
DNA Cell Biol. 1990 Apr;9(3):193-203
2340091
Bioorg Med Chem. 2003 Apr 3;11(7):1227-34
12628650
J Bacteriol. 1999 Feb;181(4):1343-7
9973365
Pharmacol Rev. 1985 Mar;37(1):25-79
2860675
Biochem Pharmacol. 2005 Jan 15;69(2):347-59
15627487
J Biol Chem. 2013 Aug 9;288(32):23447-56
23779105