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Titolo:
Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis
Autore:
Zimhony, O; Cox, JS; Welch, JT; Vilcheze, C; Jacobs, WR;
Indirizzi:
Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, Montefiore Med Ctr, Dept Microbiol & Immunol, Bronx, NY 10461 USA Yeshiva Univ Albert Einstein Coll Med Bronx NY USA 10461 nx, NY 10461 USA Yeshiva Univ Albert Einstein Coll Med, Div Infect Dis, Bronx, NY 10461 USAYeshiva Univ Albert Einstein Coll Med Bronx NY USA 10461 nx, NY 10461 USA SUNY Albany, Dept Chem, Albany, NY 12222 USA SUNY Albany Albany NY USA 12222 Y Albany, Dept Chem, Albany, NY 12222 USA
Titolo Testata:
NATURE MEDICINE
fascicolo: 9, volume: 6, anno: 2000,
pagine: 1043 - 1047
SICI:
1078-8956(200009)6:9<1043:PITEFA>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; VITRO ANTIMYCOBACTERIAL ACTIVITY; SHORT-COURSE CHEMOTHERAPY; VAR BOVIS BCG; PYRAZINOIC ACID; MYCOLIC ACIDS; GENE; SYNTHASE; RESISTANCE; MUTATIONS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Jacobs, WR Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, Montefiore Med Ctr, Dept Microbiol & Immunol, Bronx, NY 10461 USA Yeshiva Univ Albert Einstein Coll Med Bronx NY USA 10461 1 USA
Citazione:
O. Zimhony et al., "Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis", NAT MED, 6(9), 2000, pp. 1043-1047

Abstract

Tuberculosis treatment is shortened to six months by the indispensable addition of pyrazinamide (PZA) to the drug regimen that includes isoniazid andrifampin(1,2). PZA is a pro-drug of pyrazinoic acid (POA) (ref. 3), whose target of action has never been identified. Although PZA is active only against Mycobacterium tuberculosis, the PZA analog 5-chloro-pyrazinamide (5-CI-PZA) displays a broader range of anti-mycobacterial activity(4). We have found that the eukaryotic-like fas1 gene(5) (encoding fatty acid synthetase I, FASI) from M. avium, M. bovis BCG or M. tuberculosis confers resistance to 5-CI-PZA when present on multi-copy vectors in M, smegmatis. 5-CI-PZA and PZA markedly inhibited the activity of M, tuberculosis FASI, the biosynthesis of C-16 to C-24/C26 fatty acids from acetyl-CoA (ref.6). Importantly, PZA inhibited FASI in M. tuberculosis in correlation with PZA susceptibility. These results indicate that FASI is a primary target of action for PZA in M. tuberculosis. Further characterization of FASI as a drug target for PZA may allow the development of new drugs to shorten the therapy against M. tuberculosis and may provide more options for treatment against M. bovis, M. avium and drug resistant M. tuberculosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 13:48:23