Pyrazinamide and Pyrazinoic Acid Activity against Tubercle Bacilli in Cultured Human Macrophages and in the BACTEC System
Identifieur interne : 003016 ( Main/Exploration ); précédent : 003015; suivant : 003017Pyrazinamide and Pyrazinoic Acid Activity against Tubercle Bacilli in Cultured Human Macrophages and in the BACTEC System
Auteurs : Max Salfinger [Suisse] ; Alfred J. Crowle ; L. Barth RellerSource :
- Journal of Infectious Diseases [ 0022-1899 ] ; 1990.
Abstract
Pyrazinamide (PZA) has becomean essential component of current 6-month regimens for therapy of tuberculosis. Susceptible strains of tubercle bacilliconvert PZA to pyrazinoic acid (POA)through pyrazinamidase (PZase), which resistant strains and Mycobacterium bovis bacilleCalmette-Guerin lack. PZA susceptibility results obtained in cultured human macrophages were compared with those in the broth BACTEC system with 7H12 medium at pH 6.0 for strains known to bePZasepositive or -negative. Although added PDA was unable to inhibit tubercle bacilli in cultured macrophages, it was able to inhibit them at very high concentrations in the BACTEC broth. Intracellularly formed PDA would not be able to escape from the macrophage, and therefore would accumulate sufficiently to lower pH to toxic levels for tubercle bacilli. The results suggest that the cultured macrophages contribute actively or passively to the effectiveness of PZA, such as through the proposed mechanism of low pH generated by PZase in the phagolysosomes.
Url:
DOI: 10.1093/infdis/162.1.201
Affiliations:
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Crowle</name><affiliation><wicri:noCountry code="subField">Denver</wicri:noCountry></affiliation></author><author><name sortKey="Reller, L Barth" sort="Reller, L Barth" uniqKey="Reller L" first="L. Barth" last="Reller">L. Barth Reller</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Infectious Diseases</title><title level="j" type="abbrev">J Infect Dis.</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date when="1990-07">1990</date><biblScope unit="vol">162</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="201">201</biblScope><biblScope unit="page" to="207">207</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Pyrazinamide (PZA) has becomean essential component of current 6-month regimens for therapy of tuberculosis. Susceptible strains of tubercle bacilliconvert PZA to pyrazinoic acid (POA)through pyrazinamidase (PZase), which resistant strains and Mycobacterium bovis bacilleCalmette-Guerin lack. PZA susceptibility results obtained in cultured human macrophages were compared with those in the broth BACTEC system with 7H12 medium at pH 6.0 for strains known to bePZasepositive or -negative. Although added PDA was unable to inhibit tubercle bacilli in cultured macrophages, it was able to inhibit them at very high concentrations in the BACTEC broth. Intracellularly formed PDA would not be able to escape from the macrophage, and therefore would accumulate sufficiently to lower pH to toxic levels for tubercle bacilli. The results suggest that the cultured macrophages contribute actively or passively to the effectiveness of PZA, such as through the proposed mechanism of low pH generated by PZase in the phagolysosomes.</div></front></TEI><affiliations><list><country><li>Suisse</li></country></list><tree><noCountry><name sortKey="Crowle, Alfred J" sort="Crowle, Alfred J" uniqKey="Crowle A" first="Alfred J." last="Crowle">Alfred J. Crowle</name><name sortKey="Reller, L Barth" sort="Reller, L Barth" uniqKey="Reller L" first="L. Barth" last="Reller">L. Barth Reller</name></noCountry><country name="Suisse"><noRegion><name sortKey="Salfinger, Max" sort="Salfinger, Max" uniqKey="Salfinger M" first="Max" last="Salfinger">Max Salfinger</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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