Yimcharoen Manita, Saikaew Sukanya, Wattananandkul Usanee, Phunpae Ponrut, Intorasoot Sorasak, Tayapiwatana Chatchai, Butr-Indr Bordin
Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Antibiotics (Basel). 2023 May 5;12(5):852. doi: 10.3390/antibiotics12050852.
Isoniazid (INH) is an antibiotic that is widely used to treat tuberculosis (TB). Adaptation to environmental stress is a survival strategy for and is associated with antibiotic resistance development. Here, mycobacterial adaptation following INH treatment was studied using a multi-stress system (MS), which mimics host-derived stress. Mtb H37Rv (drug-susceptible), mono-isoniazid resistant (INH-R), mono-rifampicin resistant (RIF-R), and multidrug-resistant (MDR) strains were cultivated in the MS with or without INH. The expression of stress-response genes (, , , and ) and lipoarabinomannan (LAM)-related genes (, , , , , and ), which play important roles in the host-pathogen interaction, were measured using real-time PCR. The different adaptations of the drug-resistant (DR) and drug-susceptible (DS) strains were presented in this work. and were up-regulated in the DR strains in the MS, implying their roles as markers of virulence and potential drug targets. In the presence of INH, , , and were up-regulated in the INH-R and RIF-R strains, while and LAM-related genes were up-regulated in the H37Rv strain. This study demonstrates the complexity of mycobacterial adaptation through stress response regulation and LAM expression in response to INH under the MS, which could potentially be applied for TB treatment and monitoring in the future.
异烟肼（INH）是一种广泛用于治疗结核病（TB）的抗生素。适应环境压力是一种生存策略，与抗生素耐药性的产生有关。在此，使用模拟宿主来源压力的多应激系统（MS）研究了异烟肼治疗后分枝杆菌的适应性。将结核分枝杆菌H37Rv（药物敏感株）、单异烟肼耐药（INH-R）株、单利福平耐药（RIF-R）株和耐多药（MDR）株在有或无异烟肼的MS中培养。使用实时PCR检测在宿主-病原体相互作用中起重要作用的应激反应基因（、、、和）和脂阿拉伯甘露聚糖（LAM）相关基因（、、、、和）的表达。这项工作展示了耐药（DR）株和药物敏感（DS）株的不同适应性。在MS中，和在DR株中上调，这意味着它们作为毒力标志物和潜在药物靶点的作用。在异烟肼存在的情况下，、和在INH-R和RIF-R株中上调，而和LAM相关基因在H37Rv株中上调。本研究证明了在MS下分枝杆菌通过应激反应调节和LAM表达对异烟肼产生适应性的复杂性，这在未来可能应用于结核病的治疗和监测。
