Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Av. Universidad 3000, Coyoacán, Copilco Universidad, 04510 Mexico City, DF, Mexico.
Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Av. Universidad 3000, Coyoacán, Copilco Universidad, 04510 Mexico City, DF, Mexico; Laboratorio de Infectología, Instituto Nacional de Rehabilitación, Mexico City, Mexico.
Int J Antimicrob Agents. 2017 Jan;49(1):88-92. doi: 10.1016/j.ijantimicag.2016.08.022. Epub 2016 Oct 7.
Acinetobacter baumannii is an emergent opportunistic bacterial pathogen responsible for recalcitrant infections owing to its high intrinsic tolerance to most antibiotics; therefore, suitable strategies to treat these infections are needed. One plausible approach is the repurposing of drugs that are already in use. Among them, anticancer drugs may be especially useful due their cytotoxic activities and ample similarities between bacterial infections and growing tumours. In this work, the effectiveness of four anticancer drugs on the growth of A. baumannii ATTC BAA-747 was evaluated, including the antimetabolite 5-fluorouracil and three DNA crosslinkers, namely cisplatin, mitomycin C (MMC) and merphalan. MMC was the most effective drug, having a minimum inhibitory concentration for 50% of growth in Luria-Bertani medium at ca. 7 µg/mL and completely inhibiting growth at 25 µg/mL. Hence, MMC was tested against a panel of 21 clinical isolates, including 18 multidrug-resistant (MDR) isolates, 3 of which were sensitive only to colistin. The minimum inhibitory concentrations and minimum bactericidal concentrations of MMC in all tested strains were found to be similar to those of A. baumannii ATCC BAA-747, and MMC also effectively killed stationary-phase, persister and biofilm cells. Moreover, MMC was able to increase survival of the insect larvae Galleria mellonella against an otherwise lethal A. baumannii infection from 0% to ≥53% for the antibiotic-sensitive A. baumannii ATCC BAA-747 strain and the MDR strains A560 and A578. Therefore, MMC is highly effective at killing the emergent opportunistic pathogen A. baumannii.
鲍曼不动杆菌是一种新兴的机会性细菌病原体，由于其对大多数抗生素具有较高的固有耐受性，因此导致其感染难以治疗；因此，需要寻找合适的策略来治疗这些感染。一种可行的方法是重新利用已有的药物。其中，抗癌药物可能特别有用，因为它们具有细胞毒性作用，并且细菌感染和肿瘤生长之间存在大量相似之处。在这项工作中，评估了四种抗癌药物对鲍曼不动杆菌 ATTC BAA-747 生长的影响，包括代谢物 5-氟尿嘧啶和三种 DNA 交联剂，即顺铂、丝裂霉素 C（MMC）和美法仑。MMC 是最有效的药物，在 Luria-Bertani 培养基中的最低抑菌浓度（MIC50）约为 7μg/mL，在 25μg/mL 时完全抑制生长。因此，MMC 被测试了 21 株临床分离株，包括 18 株多药耐药（MDR）株，其中 3 株仅对粘菌素敏感。在所有测试菌株中，MMC 的最低抑菌浓度和最低杀菌浓度与鲍曼不动杆菌 ATCC BAA-747 相似，MMC 还能有效杀死静止期、持久期和生物膜细胞。此外，MMC 能够提高昆虫幼虫家蚕对致命性鲍曼不动杆菌感染的存活率，从抗生素敏感的鲍曼不动杆菌 ATCC BAA-747 菌株和 MDR 菌株 A560 和 A578 的 0%增加到≥53%。因此，MMC 对新兴的机会性病原体鲍曼不动杆菌具有高度的杀菌作用。
