Rastogi N, Goh K S, David H L
Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Paris, France.
Antimicrob Agents Chemother. 1990 May;34(5):759-64. doi: 10.1128/AAC.34.5.759.
Treatment of infections caused by Mycobacterium avium complex bacteria still remains a challenge since these organisms are resistant to a majority of antituberculous drugs. M. avium is very often linked with acquired immune deficiency syndrome-associated opportunistic infections. We earlier suggested that one of the strategies for circumventing multiple-drug resistance might be the enhancement of M. avium drug susceptibility by inhibiting the synthesis of the outermost layer of its envelope, which appears to act as an exclusionary barrier for drugs. In this investigation, we have examined this strategy by simultaneously using drugs and the following inhibitors of the M. avium cell envelope: m-fluoro-phenylalanine (an inhibitor of mycoside-C biosynthesis), DL-norleucine (an inhibitor of transmethylation reactions), ethambutol (an inhibitor of arabinogalactan synthesis), EDTA (a divalent-ion chelator), and colistin (an inducer of membrane flux of divalent cations). All the drugs were used in concentrations which were low enough for a possible medical application to be foreseen. This approach, tested on seven strains of the M. avium complex, showed that both m-fluoro-phenylalanine and ethambutol were interesting candidates because they caused significant enhancement of M. avium drug susceptibility.
鸟分枝杆菌复合群细菌引起的感染治疗仍然是一项挑战，因为这些微生物对大多数抗结核药物具有抗性。鸟分枝杆菌常常与获得性免疫缺陷综合征相关的机会性感染有关。我们之前曾提出，规避多重耐药性的策略之一可能是通过抑制其包膜最外层的合成来增强鸟分枝杆菌对药物的敏感性，其包膜似乎充当了药物的排斥屏障。在本研究中，我们通过同时使用药物和以下鸟分枝杆菌细胞包膜抑制剂来检验这一策略：间氟苯丙氨酸（霉菌酸-C生物合成抑制剂）、DL-正亮氨酸（转甲基化反应抑制剂）、乙胺丁醇（阿拉伯半乳聚糖合成抑制剂）、EDTA（二价离子螯合剂）和多粘菌素（二价阳离子膜通量诱导剂）。所有药物的使用浓度都足够低，以便可以预见其可能的医学应用。在七株鸟分枝杆菌复合群菌株上测试的这种方法表明，间氟苯丙氨酸和乙胺丁醇都是有吸引力的候选药物，因为它们能显著增强鸟分枝杆菌对药物的敏感性。
