Mitomycin C as an Anti-Persister Strategy against Klebsiella pneumoniae: Toxicity and Synergy Studies

Autor: Olga Pacios, Soraya Herrera-Espejo, Lucía Armán, Clara Ibarguren-Quiles, Lucía Blasco, Inés Bleriot, Laura Fernández-García, Concha Ortiz-Cartagena, María Paniagua, Antonio Barrio-Pujante, Belén Aracil, José Miguel Cisneros, María Eugenia Pachón-Ibáñez, María Tomás
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Antibiotics, Vol 13, Iss 9, p 815 (2024)
Druh dokumentu: article
ISSN: 2079-6382
DOI: 10.3390/antibiotics13090815
Popis: 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 Klebsiella pneumoniae 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 K. pneumoniae 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.
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