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In Vivo Activity of Metal Complexes Containing 1,10-Phenanthroline and 3,6,9-Trioxaundecanedioate Ligands against <i>Pseudomonas aeruginosa</i> Infection in <i>Galleria mellonella</i> Larvae
oleh: Megan O’Shaughnessy, Magdalena Piatek, Pauraic McCarron, Malachy McCann, Michael Devereux, Kevin Kavanagh, Orla Howe
Format: | Article |
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Diterbitkan: | MDPI AG 2022-01-01 |
Deskripsi
Drug-resistant <i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> from CF patients in vitro. Herein, we present the in vivo efficacy of {[Cu(3,6,9-tdda)(phen)<sub>2</sub>]·<sub>3</sub>H<sub>2</sub>O·EtOH}<sub>n</sub> (Cu-tdda-phen), {[Mn(3,6,9-tdda)(phen)<sub>2</sub>]·<sub>3</sub>H<sub>2</sub>O·EtOH}<sub>n</sub> (Mn-tdda-phen) and [Ag<sub>2</sub>(3,6,9-tdda)(phen)<sub>4</sub>]·EtOH (Ag-tdda-phen) (tddaH<sub>2</sub> = 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 <i>Galleria mellonella</i> infected with clinical isolates and laboratory strains of <i>P. aeruginosa</i>. <i>G. mellonella</i> 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 <i>transferrin</i> and <i>inducible metallo-proteinase inhibitor</i>. The amalgamation of metal-tdda-phen complexes and gentamicin further intensified this response at lower concentrations, clearing a <i>P. aeruginosa</i> 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.