Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy.
Department of Biotechnology, Chemistry, and Pharmacy, DoE Department of Excellence 2018-2022, University of Siena, Siena, Italy.
Arch Pharm (Weinheim). 2022 Aug;355(8):e2100492. doi: 10.1002/ardp.202100492. Epub 2022 May 9.
Nontuberculous mycobacteria (NTM) comprise several ubiquitous, environmentally localized bacteria that may be responsible for serious human diseases. NTM-associated pulmonary infections largely affect individuals with underlying respiratory disease or chronic disease and immunosuppressed patients. Mycobacterium simiae and M. abscessus are two NTMs responsible for lung disease in immunocompetent and immunocompromised individuals. In this study, two NTM strains were isolated from two patients admitted to an Italian hospital and were identified as M. simiae and M. abscessus. The two NTMs were tested for drug susceptibility against different antibiotics. To restore drug susceptibility, a new series of 2-aryl-3-phenoxymethyl-quinoxaline derivatives (QXs) was designed, synthesized, and investigated as efflux pump inhibitors (EPIs) against two clinical isolates of the above-cited NTMs, evaluating how EPIs can influence the drug minimal inhibitory concentration values and, therefore, the activity. The different\ resistance levels tracked in the clinical strains were reduced by EPIs, and in several cases, the susceptibility was completely restored. QXs also resulted as potential chemical probes to be used in drug susceptibility tests to identify the resistance origin when detected.
非结核分枝杆菌（NTM）包括几种广泛存在于环境中的细菌，它们可能导致严重的人类疾病。与 NTM 相关的肺部感染主要影响有潜在呼吸道疾病或慢性疾病和免疫抑制患者的个体。猿分枝杆菌和脓肿分枝杆菌是两种导致免疫功能正常和免疫功能低下个体肺部疾病的 NTM。在这项研究中，从两名入住意大利医院的患者中分离出了两种 NTM 菌株，并鉴定为猿分枝杆菌和脓肿分枝杆菌。对两种 NTM 进行了针对不同抗生素的药敏试验。为了恢复药物敏感性，设计、合成了一系列新的 2-芳基-3-苯氧甲基-喹喔啉衍生物（QXs），并作为外排泵抑制剂（EPIs）对上述两种临床分离株进行了研究，评估了 EPIs 如何影响药物最小抑菌浓度值，从而影响活性。EPIs 降低了临床菌株中检测到的不同耐药水平，在某些情况下，还完全恢复了敏感性。QXs 还可作为潜在的化学探针，用于药物敏感性试验，以在检测到耐药性时确定耐药性的起源。
