Antibiotics (Aug 2024)

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

  • 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

DOI
https://doi.org/10.3390/antibiotics13090815
Journal volume & issue
Vol. 13, no. 9
p. 815

Abstract

Read online

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.

Keywords