Microorganisms (Sep 2023)

Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired <i>Staphylococcus aureus</i> Infections

  • Veronica Folliero,
  • Federica Dell’Annunziata,
  • Biagio Santella,
  • Emanuela Roscetto,
  • Carla Zannella,
  • Nicoletta Capuano,
  • Alessandro Perrella,
  • Anna De Filippis,
  • Giovanni Boccia,
  • Maria Rosaria Catania,
  • Massimiliano Galdiero,
  • Gianluigi Franci

DOI
https://doi.org/10.3390/microorganisms11092242
Journal volume & issue
Vol. 11, no. 9
p. 2242

Abstract

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The emergence of multidrug-resistant strains requires the urgent discovery of new antibacterial drugs. In this context, an antibacterial screening of a subset of anthelmintic avermectins against gram-positive and gram-negative strains was performed. Selamectin completely inhibited bacterial growth at 6.3 μg/mL concentrations against reference gram-positive strains, while no antibacterial activity was found against gram-negative strains up to the highest concentration tested of 50 μg/mL. Given its relevance as a community and hospital pathogen, further studies have been performed on selamectin activity against Staphylococcus aureus (S. aureus), using clinical isolates with different antibiotic resistance profiles and a reference biofilm-producing strain. Antibacterial studies have been extensive on clinical S. aureus isolates with different antibiotic resistance profiles. Mean MIC90 values of 6.2 μg/mL were reported for all tested S. aureus strains, except for the macrolide-resistant isolate with constitutive macrolide-lincosamide-streptogramin B resistance phenotype (MIC90 9.9 μg/mL). Scanning Electron Microscopy (SEM) showed that selamectin exposure caused relevant cell surface alterations. A synergistic effect was observed between ampicillin and selamectin, dictated by an FIC value of 0.5 against methicillin-resistant strain. Drug administration at MIC concentration reduced the intracellular bacterial load by 81.3%. The effect on preformed biofilm was investigated via crystal violet and confocal laser scanning microscopy. Selamectin reduced the biofilm biomass in a dose-dependent manner with minimal biofilm eradication concentrations inducing a 50% eradication (MBEC50) at 5.89 μg/mL. The cytotoxic tests indicated that selamectin exhibited no relevant hemolytic and cytotoxic activity at active concentrations. These data suggest that selamectin may represent a timely and promising macrocyclic lactone for the treatment of S. aureus infections.

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