In Vivo Activity of Metal Complexes Containing 1,10-Phenanthroline and 3,6,9-Trioxaundecanedioate Ligands against Pseudomonas aeruginosa Infection in Galleria mellonella Larvae.
Megan O'ShaughnessyMagdalena PiatekPauraic McCarronMalachy McCannMichael DevereuxKevin KavanaghOrla HowePublished in: Biomedicines (2022)
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 ]· 3 H 2 O·EtOH} n (Cu-tdda-phen), {[Mn(3,6,9-tdda)(phen) 2 ]· 3 H 2 O·EtOH} n (Mn-tdda-phen) and [Ag 2 (3,6,9-tdda)(phen) 4 ]·EtOH (Ag-tdda-phen) (tddaH 2 = 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.
Keyphrases
- pseudomonas aeruginosa
- drug resistant
- cystic fibrosis
- end stage renal disease
- immune response
- chronic kidney disease
- acinetobacter baumannii
- ejection fraction
- newly diagnosed
- multidrug resistant
- peritoneal dialysis
- prognostic factors
- staphylococcus aureus
- biofilm formation
- genome wide
- candida albicans
- patient reported outcomes
- zika virus
- toll like receptor
- transcription factor
- aedes aegypti
- extracorporeal membrane oxygenation
- amino acid