Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
J Antimicrob Chemother. 2010 Jul;65(7):1424-7. doi: 10.1093/jac/dkq145. Epub 2010 Apr 30.
To determine the effect of 8-hydroxyquinoline (8HQ) on non-replicating Mycobacterium tuberculosis (Mtb) in comparison with its reported effect on replicating Mtb.
The MIC of 8HQ for replicating H37Rv Mtb was determined by microdilution in 7H9 broth. Bactericidal activity was determined by exposing H37Rv Mtb to 8HQ for 4 days under conditions that otherwise allowed exponential replication (20% O(2), pH 6.6) and conditions under which replication was precluded: 1% O(2), pH 6.6; 20% O(2), pH 5.5; or 20% O(2), pH 5.5, 0.5 mM sodium nitrite. Serial dilutions were plated on 7H11 agar to quantify cfu. Frequency of resistance (FOR) was determined with >10(9) bacteria plated on 7H9 agar plates containing 2x MIC 8HQ.
8HQ was active against replicating Mtb (MIC 2.5 microM, 0.36 mg/L). Under both replicating and non-replicating conditions, cfu were reduced in 4 days by > or = 5 log(10) at the highest concentration tested (10 microM). Bactericidal activity was maximal at low pH, where 8HQ reduced cfu by 1-1.5 log(10) at 1 microM. We were unable to recover any 8HQ-resistant colonies.
This study demonstrates that 8HQ has bactericidal activity of comparable potency against non-replicating and replicating Mtb, a property not observed for anti-infective agents currently approved for treatment of tuberculosis, and a very low FOR. Drugs with these properties are urgently needed to shorten the course of treatment for both active and latent tuberculosis.
与 8-羟基喹啉（8HQ）对复制型结核分枝杆菌（Mtb）的报道作用相比，确定其对非复制型 Mtb 的影响。
通过在 7H9 肉汤中进行微量稀释来确定 8HQ 对复制型 H37Rv Mtb 的 MIC。通过在允许指数复制的条件下（20% O（2），pH6.6）和复制被排除的条件下（1% O（2），pH6.6；20% O（2），pH5.5；或 20% O（2），pH5.5，0.5 mM 亚硝酸钠），使 H37Rv Mtb 暴露于 8HQ 4 天，来确定杀菌活性。对 7H11 琼脂进行连续稀释以定量 CFU。通过将>10（9）个细菌接种在含有 2xMIC8HQ 的 7H9 琼脂平板上来确定耐药频率（FOR）。
8HQ 对复制型 Mtb 有效（MIC2.5 microM，0.36 mg/L）。在最高测试浓度（10 microM）下，在复制和非复制条件下，4 天内 CFU 减少了>或=5log（10）。在低 pH 值下杀菌活性最大，其中 8HQ 在 1 microM 时使 CFU 减少 1-1.5log（10）。我们无法恢复任何 8HQ 抗性菌落。
本研究表明，8HQ 对非复制型和复制型 Mtb 具有相当的杀菌活性，这一特性在目前批准用于治疗结核病的抗感染药物中并未观察到，且 FOR 非常低。迫切需要具有这些特性的药物来缩短活动性和潜伏性结核病的治疗疗程。
