In Vivo Activity of Metal Complexes Containing 1,10-Phenanthroline and 3,6,9-Trioxaundecanedioate Ligands against Pseudomonas aeruginosa Infection in Galleria mellonella Larvae

Authors

Megan O'shaughnessy, Technological University DublinFollow
Magdalena Piatek, National University of Ireland, MaynoothFollow
Pauraic McCarron, Technological University DublinFollow
Malachy McCann, National University of Ireland, MaynoothFollow
Michael Devereux, Technological University DublinFollow
Kevin Kavanagh, National University of Ireland, MaynoothFollow
Orla L. Howe, Technological University DublinFollow

Document Type

Article

Rights

Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence

Disciplines

1.6 BIOLOGICAL SCIENCES, 3.3 HEALTH SCIENCES

Publication Details

Open access

https://www.mdpi.com/2227-9059/10/2/222

Abstract

Drug-resistant Pseudomonas aeruginosa 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 P. aeruginosa from CF patients in vitro. Herein, we present the in vivo efficacy of {[Cu(3,6,9-tdda)(phen)₂]·₃H₂O·EtOH}_n (Cu-tdda-phen), {[Mn(3,6,9-tdda)(phen)₂]·₃H₂O·EtOH}_n (Mn-tdda-phen) and [Ag₂(3,6,9-tdda)(phen)₄]·EtOH (Ag-tdda-phen) (tddaH₂ = 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 Galleria mellonella infected with clinical isolates and laboratory strains of P. aeruginosa. G. mellonella 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 transferrin and inducible metallo-proteinase inhibitor. The amalgamation of metal-tdda-phen complexes and gentamicin further intensified this response at lower concentrations, clearing a P. aeruginosa 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.

DOI

https://doi.org/10.3390/biomedicines10020222

Recommended Citation

O’Shaughnessy M, Piatek M, McCarron P, McCann M, Devereux M, Kavanagh K, Howe O. In Vivo Activity of Metal Complexes Containing 1,10-Phenanthroline and 3,6,9-Trioxaundecanedioate Ligands against Pseudomonas aeruginosa Infection in Galleria mellonella Larvae. Biomedicines. 2022; 10(2):222. DOI: 10.3390/biomedicines10020222

Funder

Science Foundation Ireland; European Regional Development Fund