Sirichoat Auttawit, Kham-Ngam Irin, Kaewprasert Orawee, Ananta Pimjai, Wisetsai Awat, Lekphrom Ratsami, Faksri Kiatichai
Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Research and Diagnostic Center for Emerging Infectious Diseases, Khon Kaen University, Khon Kaen, Thailand.
PeerJ. 2021 Oct 26;9:e12391. doi: 10.7717/peerj.12391. eCollection 2021.
Infection with is usually chronic and is associated with clarithromycin resistance. Increasing drug resistance is a major public-health problem and has led to the search for new antimycobacterial agents. We evaluated the antimycobacterial activity, toxicity, and synergistic effects of several plant secondary metabolites against .
Twenty-three compounds were evaluated for antimycobacterial activity against thirty clinical isolates by broth microdilution to determine their minimum inhibitory concentration (MIC) values. Toxicity was evaluated using red and white blood cells (RBCs and WBCs). The compounds were used in combination with clarithromycin to investigate the possibility of synergistic activity.
Five out of twenty-three compounds (RL008, RL009, RL011, RL012 and RL013) exhibited interesting antimycobacterial activity against , with MIC values ranging from <1 to >128 μg/mL. These extracts did not induce hemolytic effect on RBCs and displayed low toxicity against WBCs. The five least-toxic compounds were tested for synergism with clarithromycin against seven isolates with inducible clarithromycin resistance and seven with acquired clarithromycin resistance. The best synergistic results against these isolates were observed for RL008 and RL009 (8/14 isolates; 57%).
This study demonstrated antimycobacterial and synergistic activities of pure compounds extracted from medicinal plants against clarithromycin-resistant . This synergistic action, together with clarithromycin, may be effective for treating infections and should be further studied for the development of novel antimicrobial agents.
感染通常为慢性，并与克拉霉素耐药性相关。耐药性增加是一个主要的公共卫生问题，促使人们寻找新的抗分枝杆菌药物。我们评估了几种植物次生代谢产物对的抗分枝杆菌活性、毒性和协同作用。
通过肉汤微量稀释法评估23种化合物对30株临床分离株的抗分枝杆菌活性，以确定其最低抑菌浓度（MIC）值。使用红细胞和白细胞（RBC和WBC）评估毒性。将这些化合物与克拉霉素联合使用，研究协同活性的可能性。
23种化合物中的5种（RL008、RL009、RL011、RL012和RL013）对表现出有趣的抗分枝杆菌活性，MIC值范围为<1至>128μg/mL。这些提取物对RBCs未诱导溶血作用，对WBCs显示低毒性。对5种毒性最低的化合物测试了与克拉霉素对7株诱导型克拉霉素耐药和7株获得性克拉霉素耐药分离株的协同作用。对这些分离株观察到的最佳协同结果是RL008和RL009（8/14株；57%）。
本研究证明了从药用植物中提取的纯化合物对克拉霉素耐药的具有抗分枝杆菌和协同活性。这种与克拉霉素的协同作用可能对治疗感染有效，应进一步研究以开发新型抗菌剂。
