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

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.