Diphenyl diselenide suppresses key virulence factors of Candida krusei, a neglected fungal pathogen

Abstract

Candida krusei is a candidiasis etiological agent of relevance in the clinical setting because of its intrinsic resistance to fluconazole. Also, it has opened up new paths in the area of alternative therapeutic techniques. This project demonstrated the effects of diphenyl diselenide (PhSe)₂ and p-cloro diphenyl diselenide (pCl-PhSe)₂, two organochalcogen compounds, on relevant virulence factors for the early stage of the C. krusei host interaction and infection process. Both compounds inhibited adherence of C. krusei to both polystyrene surfaces and cervical epithelial cells and biofilm formation; the structure of the biofilm was also changed in a dose-dependent manner. In addition, both compounds inhibited C. krusei growth, but (PhSe)₂ significantly increased the time duration of the lag phase and delayed the start of the exponential phase in growth kinetics. (PhSe)₂ has more potential antifungal activity than (pCl-PhSe)₂ in inhibiting the adherence to epithelial cells, biofilm formation, and growth of C. krusei.

Graphical Abstract

Keywords:

• Candida krusei
• Organochalcogen compound
• Antifungal activity
• Adhesion cell
• Virulence factors

Acknowledgements

The authors would like to thank the technical group of the Laboratory of Experimental Morphophysiology (UFABC) and Biochemistry Laboratory Applied to Biomedical Engineering (UNIVAP) for assistance in the experimental procedures. Thanks are also due to the administrative-technical group of UFABC and UNIVAP for secretarial assistance.

Disclosure statement

The authors have no financial, personal, or other conflicts of interest related to this work.

Ethical approval

Candida krusei (ATCC #6258) was used to test the drug's antifungal properties. All Candida species investigations were carried out in compliance with the Brazilian Health Regulatory Agency's (ANVISA) technical norms (# M27-A2), an autarchy linked to the Ministry of Health and part of the Brazilian National Health System (SUS). HeLa cells from human cervical epithelial cells (CCL2, from the American Type Culture Collection - ATCC, Manassas, VA, USA) and the Vero cell line from African green monkey kidney cells (Cercopithecus aethiops - CCIAL 057, provided by the Adolfo Lutz Institute, São Paulo, Brazil) were also used in mammalian cell tests. In these cases, our experiments were also developed under the application of good laboratory practice (GLP) to culture collections of microbial and cell cultures (Stevenson and Jong 1992).

Informed consent

We have obtained permission from all the authors and we declare that the material has not been published in whole or in part elsewhere, nor is the paper currently being considered for publication elsewhere.

Additional information

Funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001.