Gandra, Rafael M. and McCarron, Pauraic and Viganor, Livia and Fernandes, Mariana Farias and Kavanagh, Kevin and McCann, Malachy and Branquinha, Marta H. and Santos, Andre L. S. and Howe, Orla and Devereux, Michael (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). ISSN 1664-302X

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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.

Item Type:	Article
Additional Information:	© 2020 Gandra, McCarron, Viganor, Fernandes, Kavanagh, McCann, Branquinha, Santos, Howe and Devereux. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/about/cclicenses/ ). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Citation: Gandra RM, McCarron P, Viganor L, Fernandes MF, Kavanagh K, McCann M, Branquinha MH, Santos ALS, Howe O and Devereux M (2020) In vivo Activity of Copper(II), Manganese(II), and Silver(I) 1,10-Phenanthroline Chelates Against Candida haemulonii Using the Galleria mellonella Model. Front. Microbiol. 11:470. doi: 10.3389/fmicb.2020.00470 Funding: This study was supported by grants and fellowships from the Government of Ireland International Education Scholarships Programme, the Research Brazil Ireland (RBI) mobility initiative funded under the Science Foundation Ireland (SFI) International Strategic Cooperation Award (ISCA) Programme and the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and Coordenacão de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – Finance Code 001).
Keywords:	Candida haemulonii; metal-1,10-phenanthroline chelates; Galleria mellonella; antifungal activity; immunomodulation;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Chemistry
Item ID:	13677
Identification Number:	https://doi.org/10.3389/fmicb.2020.00470
Depositing User:	Dr. Kevin Kavanagh
Date Deposited:	26 Nov 2020 17:16
Journal or Publication Title:	Frontiers in Microbiology
Publisher:	Frontiers
Refereed:	Yes
Funders:	Government of Ireland International Education Scholarships Programme, Research Brazil Ireland (RBI), Science Foundation Ireland (SFI), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Coordenacão de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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