In Vivo Activity of Metal Complexes Containing 1,10-Phenanthroline and 3,6,9-Trioxaundecanedioate Ligands Against Infection in Larvae

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2022 Feb 25

PMID 35203432

Authors

Megan OShaughnessy

Magdalena Piatek

Pauraic McCarron

Malachy McCann

Michael Devereux

Kevin Kavanagh

Orla Howe

Affiliations

Soon will be listed here.

Abstract

Drug-resistant is rapidly developing resulting in a serious global threat. Immunocompromised patients are specifically at risk, especially those with cystic fibrosis (CF). Novel metal complexes incorporating 1,10-phenanthroline (phen) ligands have previously demonstrated antibacterial and anti-biofilm effects against resistant from CF patients in vitro. Herein, we present the in vivo efficacy of {[Cu(3,6,9-tdda)(phen)]·HO·EtOH} (Cu-tdda-phen), {[Mn(3,6,9-tdda)(phen)]·HO·EtOH} (Mn-tdda-phen) and [Ag(3,6,9-tdda)(phen)]·EtOH (Ag-tdda-phen) (tddaH = 3,6,9-trioxaundecanedioic acid). Individual treatments of these metal-tdda-phen complexes and in combination with the established antibiotic gentamicin were evaluated in vivo in larvae of infected with clinical isolates and laboratory strains of . were able to tolerate all test complexes up to 10 µg/larva. In addition, the immune response was affected by stimulation of immune cells (hemocytes) and genes that encode for immune-related peptides, specifically and . The amalgamation of metal-tdda-phen complexes and gentamicin further intensified this response at lower concentrations, clearing a infection that were previously resistant to gentamicin alone. Therefore this work highlights the anti-pseudomonal capabilities of metal-tdda-phen complexes alone and combined with gentamicin in an in vivo model.

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