Pacios Olga, Herrera-Espejo Soraya, Armán Lucía, Ibarguren-Quiles Clara, Blasco Lucía, Bleriot Inés, Fernández-García Laura, Ortiz-Cartagena Concha, Paniagua María, Barrio-Pujante Antonio, Aracil Belén, Cisneros José Miguel, Pachón-Ibáñez María Eugenia, Tomás María
Translational and Multidisciplinary Microbiology Research Group (MicroTM)-Microbiology Department, Biomedical Research Institute of A Coruña (INIBIC), A Coruña Hospital (CHUAC), University of A Coruña (UDC), 15006 A Coruña, Spain.
Mechanisms of Antimicrobial Resistance Study Group (GEMARA) on Behalf of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), 28003 Madrid, Spain.
Antibiotics (Basel). 2024 Aug 28;13(9):815. doi: 10.3390/antibiotics13090815.
The combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the lytic phage vB_KpnM-VAC13 in vitro and its safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked using both cytotoxicity assays and flow cytometry.
几种治疗策略的联合使用通常被视为降低耐药率的好方法，因为细菌相较于多药治疗，更容易克服单药治疗。当多个靶点和亚群受到影响时，这种策略尤其具有吸引力，例如持留菌细胞的情况，持留菌细胞是细菌的一个亚群，能够在抗生素暴露下短暂存活。这项工作旨在评估一种重新利用的抗癌药物丝裂霉素C与裂解性噬菌体vB_KpnM-VAC13在体外联合使用的潜力，以及其在体内小鼠模型中针对该病原体的两种临床分离株的安全性，其中一种分离株表现出亚胺培南持留菌表型。同时，我们使用人软骨细胞系T/C28a2验证了该浓度下丝裂霉素C的无毒性。使用细胞毒性测定和流式细胞术检查了这些人类细胞的活力。
