Wang Jun, Jing Wei, Shi Jin, Huo Fengmin, Shang Yuanyuan, Wang Fen, Chu Naihui, Pang Yu
Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
Microb Drug Resist. 2021 Aug;27(8):1013-1017. doi: 10.1089/mdr.2020.0239. Epub 2021 Feb 26.
In this study, we conducted an experimental study to evaluate susceptibility of Q203 against , as well as the major pathogenic nontuberculous mycobacterial species. A total of 344 nonduplicate mycobacterium isolates were randomly selected for susceptibility testing. Overall, Q203 exhibited excellent activity against multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) isolates, whereas it showed high minimum inhibitory concentration (MIC) values for all nontuberculous mycobacteria (NTM) isolates tested. The MIC and MIC values were both 0.008 mg/L for MDR- and XDR-TB isolates, respectively. In contrast, the MIC and MIC values of four NTM species were all >16 mg/L. QcrB of , a component of the CytBC1 complex of the respiratory chain targeted by Q230, shared 89.7% amino acid sequence identity with QcrB, 87.9% with that of , and 84.0% with that of , whereas with low sequence identity observed in QcrB sequence of . Notably, the QcrBs of and contained a 10-amino acid insertion in the linker between the eighth and ninth helical region. In conclusion, our data demonstrate the bipolar distribution of Q203 MICs across mycobacterial species. Compared with the high MICs in four clinically relevant mycobacterial species, MDR- and XDR-TB isolates have extremely low MICs, indicating that Q203 is a particularly promising candidate for TB treatment. In addition, the 10-amino acid insertion within QcrBs of and may be a plausible explanation for the natural resistance to Q203 among these two species.
在本研究中，我们进行了一项实验研究，以评估Q203对[具体对象未明确]以及主要致病性非结核分枝杆菌物种的敏感性。总共随机选择了344株非重复分枝杆菌分离株进行药敏试验。总体而言，Q203对耐多药（MDR-）和广泛耐药结核病（XDR-TB）分离株表现出优异的活性，而对所有测试的非结核分枝杆菌（NTM）分离株显示出高最低抑菌浓度（MIC）值。MDR-和XDR-TB分离株的MIC和MIC值分别为0.008 mg/L。相比之下，四种NTM物种的MIC和MIC值均>16 mg/L。Q230靶向的呼吸链CytBC1复合物的组成部分[具体对象未明确]的QcrB与[具体对象未明确]的QcrB氨基酸序列同一性为89.7%，与[具体对象未明确]的为87.9%，与[具体对象未明确]的为84.0%，而在[具体对象未明确]的QcrB序列中观察到低序列同一性。值得注意的是，[具体对象未明确]和[具体对象未明确]的QcrB在第八和第九螺旋区域之间的连接区含有10个氨基酸的插入。总之，我们的数据证明了Q203 MICs在分枝杆菌物种中的双极分布。与四种临床相关分枝杆菌物种中的高MICs相比，MDR-和XDR-TB分离株的MICs极低，表明Q203是结核病治疗的一个特别有前景的候选药物。此外，[具体对象未明确]和[具体对象未明确]的QcrB内的10个氨基酸插入可能是这两个物种对Q203天然耐药的一个合理原因。
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