Preprint Article Version 1 This version is not peer-reviewed

Mitomycin C as an Anti-persister Strategy Against Klebsiella Pneumoniae: Toxicity and Synergy Studies

Version 1 : Received: 5 August 2024 / Approved: 6 August 2024 / Online: 6 August 2024 (12:44:18 CEST)

How to cite: Pacios, O.; Herrera-Espejo, S.; Armán, L.; Ibarguren-Quiles, C.; Blasco, L.; Bleriot, I.; Fernández-García, L.; Ortiz-Cartagena, C.; Paniagua, M.; Barrio Pujante, A.; Aracil, B.; Cisneros, J. M.; Pachon, M. E.; Tomás, M. Mitomycin C as an Anti-persister Strategy Against Klebsiella Pneumoniae: Toxicity and Synergy Studies. Preprints 2024, 2024080398. https://doi.org/10.20944/preprints202408.0398.v1 Pacios, O.; Herrera-Espejo, S.; Armán, L.; Ibarguren-Quiles, C.; Blasco, L.; Bleriot, I.; Fernández-García, L.; Ortiz-Cartagena, C.; Paniagua, M.; Barrio Pujante, A.; Aracil, B.; Cisneros, J. M.; Pachon, M. E.; Tomás, M. Mitomycin C as an Anti-persister Strategy Against Klebsiella Pneumoniae: Toxicity and Synergy Studies. Preprints 2024, 2024080398. https://doi.org/10.20944/preprints202408.0398.v1

Abstract

The combination of several therapeutic strategies is often seen as a good way to decrease the resistance rates, since bacteria overcome better 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 the 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 both by cytotoxicity assays and flow cytometry.

Keywords

persistence; K. pneumoniae; repurposing; mitomycin C; lytic phage; cytotoxicity

Subject

Biology and Life Sciences, Virology

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