In Vivo Activity of Copper(II), Manganese(II), and Silver(I) 1,10-Phenanthroline Chelates

Authors

Rafael M. Ghandra, Federal University of Rio De Janeiro
Pauraic McCarron, Technological University DublinFollow
Livia Viganor, Technological University DublinFollow
Mariana Farias Fernandes, Federal University of Rio de Janeiro
Kevin Kavanagh, National University of Ireland, Maynooth
Malachy McCann, National University of Ireland, Maynooth
Marta H. Branquinha, Federal University of Rio de Janeiro
André L.S. Santos, Federal University of Rio de Janeiro
Orla L. Howe, Technological University DublinFollow
Michael Devereux, Technological University DublinFollow

Document Type

Article

Rights

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

Disciplines

Microbiology

Publication Details

Frontiers in Microbiology

Abstract

Candida haemulonii 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-Candida activity against different medically relevant species. This study utilized larvae of Galleria mellonella, a widely used model of in vivo infection, to examine C. haemulonii infection characteristics in response to different copper(II), manganese(II), and silver(I) chelates containing phen, which had demonstrated potent anti-C. haemulonii activity in a previous study. The results showed that C. haemulonii virulence was influenced by inoculum size and incubation temperature, and the host G. mellonella 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 G. mellonella immune system, affecting the hemocyte number and the expression of genes encoding antifungal and immune-related peptides (e.g., inducible metalloproteinase inhibitor protein, transferrin, galiomycin, and gallerimycin). Except for [Ag2(3,6,9-tdda)(phen)4].EtOH (3,6,9-tddaH2 = 3,6,9-trioxoundecanedioic acid), all chelates were capable of affecting the fungal burden of infected larvae and the virulence of C. haemulonii in a dose-dependent manner. This work shows that copper(II), manganese(II), and silver(I) chelates containing phen with anti-C. haemulonii activity are capable of (i) inhibiting fungal proliferation during in vivo infection, (ii) priming an immune response in the G. mellonella host and (iii) affecting C. haemulonii virulence.

DOI

https://doi.org/10.3389/fmicb.2020.00470

Recommended Citation

Gandra, R., McCarron, P., Viganor, L. et al. (2020). In vivo Activity of Copper(II), Manganese(II), and Silver(I) 1,10-Phenanthroline Chelates Against Candida haemulonii Using the Galleria mellonella Model. Frontiers in Microbiology,11, 470. doi:10.3389/fmicb.2020.00470.