@misc{10481/106953,
year = {2025},
month = {9},
url = {https://hdl.handle.net/10481/106953},
abstract = {Antimicrobial resistance represents a critical global health threat, demanding innovative therapeutic strategies. In this study, we investigate the repurposing
potential of pyrvinium pamoate (PP)—a long-established anthelmintic agent—for
antibacterial applications. Comprehensive in vitro analyses revealed that while gram-negative bacteria exhibited inherent resistance due to limited drug uptake, gram-positive
pathogens, particularly within the orders Actinomycetales and Bacillales, were markedly
susceptible at low micromolar concentrations. Enhanced antibacterial efficacy was
observed when PP was combined with outer membrane-permeabilizing agents, such
as the peptide D11 or pentamidine, which facilitated increased intracellular accumulation. Additionally, the role of efflux pump activity was explored; its inhibition in
Staphylococcus aureus resulted in significant drug retention and a concomitant reduction
in minimum inhibitory concentrations, while disruption of the proton motive force
attenuated uptake. The compound demonstrated bactericidal effects against S. aureus
and a bacteriostatic profile against Pseudomonas aeruginosa when sensitized with
outer membrane permeabilizing agents. Furthermore, synergistic studies with several
antibiotics revealed the potential of PP as a valuable addition to the antimicrobial arsenal
against multidrug-resistant pathogens. These findings motivate further mechanistic
studies and clinical evaluation of PP in antimicrobial therapy. PP shows promise as
a repurposed antibacterial agent, particularly against gram-positive pathogens, with
enhanced activity against gram-negative pathogens when combined with membranepermeabilizing agents or in the presence of efflux pump inhibitors.},
organization = {Instituto de Salud Carlos III (CP21/00113; FI23/00036)},
organization = {Ministerio de Ciencia e Innovación (PID2021-127109OB-I00)},
organization = {Andalusian Board | Consejería de Salud y
Consumo, Junta de Andalucía (CSC) - (PI-0220-2024)},
organization = {Instituto de Investigación Biosanitaria de Granada (MP_ P03_2024)},
publisher = {American Society for Microbiology},
keywords = {pyrvinium pamoate},
keywords = {Antimicrobial resistance},
keywords = {Drug repurposing},
title = {Beyond antiparasitic activity: elucidating the antibacterial potency of pyrvinium pamoate},
doi = {10.1128/spectrum.02158-25},
author = {Alcaraz Martínez, Ángela and Muñoz-Báez, Paloma and Peñalver, Pablo and Morales Vega, Juan Carlos and Cebrián, Rubén},
}