Activity of Copper(II), Manganese(II), and Silver(I) 1,10-Phenanthroline Chelates Against Using the Model.

is an emerging opportunistic pathogen resistant to most antifungal drugs currently used in clinical arena. Metal complexes containing 1,10-phenanthroline (phen) chelating ligands have well-established anti- activity against different medically relevant species. This study utilized larvae of , a widely used model of infection, to examine infection characteristics in response to different copper(II), manganese(II), and silver(I) chelates containing phen, which had demonstrated potent anti- activity in a previous study. The results showed that virulence was influenced by inoculum size and incubation temperature, and the host immune response was triggered in an inoculum-dependent manner reflected by the number of circulating immune cells (hemocytes) and observance of larval melanization process. All test chelates were non-toxic to the host in concentrations up to 10 μg/larva. The complexes also affected the immune system, affecting the hemocyte number and the expression of genes encoding antifungal and immune-related peptides (e.g., , , , and ). Except for [Ag(3,6,9-tdda)(phen)].EtOH (3,6,9-tddaH = 3,6,9-trioxoundecanedioic acid), all chelates were capable of affecting the fungal burden of infected larvae and the virulence of in a dose-dependent manner. This work shows that copper(II), manganese(II), and silver(I) chelates containing phen with anti- activity are capable of (i) inhibiting fungal proliferation during infection, (ii) priming an immune response in the host and (iii) affecting virulence.