Pyrazinamide susceptibility and amidase activity of tubercle bacilli.
Pyrazinamide susceptibility and amidase activity of tubercle bacilli.
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DOI：
10.1164/arrd.1967.95.3.461
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发表时间：
1967-03
期刊：
影响因子：
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通讯作者：
K. Konno;F. Feldmann;W. Mcdermott
中科院分区：
文献类型：
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作者：
K. Konno;F. Feldmann;W. Mcdermott
吡津酰胺是烟酰胺的类似物，具有独特的特性，当结核分枝杆菌在活体内先前或同时暴露于异烟肼时，可以有规律地对大量结核分枝杆菌进行消毒[1]。在对这种灭菌现象的长期研究中(2)，少数失败似乎主要或全部归因于对吡嗪酰胺具有抗药性的结核杆菌的出现。因此，将重点放在结核杆菌对吡嗪酰胺的抗性或敏感性上，作为研究消毒现象的一种方法似乎是合适的。当在中性环境中体外测试时，人或牛来源的结核杆菌不被吡嗪酰胺或烟酰胺抑制(3)。然而，人类来源的杆菌在体外培养时，无论是在酸性环境(PH5.6)(3)中生长，还是在单核细胞内培养(4)，都有能力对任何一种药物敏感。人类杆菌(结核分枝杆菌)在体内同样被任一种药物(5，6)抑制。相比之下，牛结核杆菌(M.bovis)在体内不受任何一种药物的抑制，它们在体外缺乏在无细胞酸性介质(3)或单核细胞(4)中变得敏感的能力。牛杆菌也只显示出很低水平的酰胺酶活性，在人类杆菌中，这种酶将吡津酰胺转化为吡津酸，将烟酰胺转化为烟酸。事实上，这种差异在
Pyrazinamide, an analogue of nicotinamide, has the unique property of sterilizing large populations of M. tuberculosis with regularity when they have undergone previous or concurrent exposure to isoniazid in vivo (1). In long-term studies of this sterilization phenomenon (2), the few failures appear to be chiefly or wholly attributable to the emergence of tubercle bacilli resistant to pyrazinamide. It seemed appropriate, therefore, to focus on the resistance or susceptibility of tubercle bacilli to pyrazinamide as one approach to the study of the sterilization phenomenon. Tubercle bacilli of human or bovine origin are not inhibited by pyrazinamide or nicotinamide when tested in vitro in a neutral environment (3). Bacilli of human origin, however, have the capacity to become susceptible to either drug in vitro, when growing in either an acidic environment (pH 5.6) (3) or within monocytes in culture (4). The human bacilli (M. tuberculosis) are likewise inhibited in vivo by either drug (5, 6). By contrast, tubercle bacilli of bovine origin (M. bovis) are not inhibited in vivo by either drug and they lack the capacity to become drugsusceptible in vitro in either the cell-free acidic medium (3) or the monocytes (4). The bovine bacilli also show only a very low level of the amidase activity that in human bacilli converts pyrazinamide to pyrazinoic acid and nicotinamide to nicotinic acid. Indeed, this difference in