Abstract
Candida albicans is an opportunistic fungus that is part of the normal microflora commonly found in the human digestive tract and the normal mucosa or skin of healthy individuals. However, in immunocompromised individuals, it becomes a serious health concern and a threat to their lives and is ranked as the leading fungal infection in humans worldwide. As existing treatments for this infection are non-specific or under threat of developing resistance, there is a dire necessity to find new targets for designing specific drugs to defeat this fungus. Some authors reported the presence of the transglutaminase activity in Candida and Saccharomyces, but its identity remains unknown. We report here the phenotypic effects produced by the inhibition of transglutaminase enzymatic activity with cystamine, including growth inhibition of yeast cells, induction of autophagy in response to damage caused by cystamine, alteration of the normal yeast division pattern, changes in cell wall, and inhibition of the yeast-to-mycelium transition. The latter phenomenon was also observed in the C. albicans ATCC 26555 strain. Growth inhibition by cystamine was also determined in other Candida strains, demonstrating the importance of transglutaminase in these species. Finally, we identified enolase 1 as the cell wall protein responsible for TGase activity. After studying the inhibition of enzymatic activities with anti-CaEno1 antibodies and through bioinformatics studies, we suggest that the enolase and transglutaminase catalytic sites are localized in different domains of the protein. The aforementioned data indicate that TGase/Eno1 is a putative target for designing new drugs to control C. albicans infection.
Highlights
Candida albicans is an opportunistic fungus that is part of the normal microflora commonly found in the human digestive tract and the normal mucosa or skin of healthy individuals
C. albicans is characterized by a complex interplay with its host by the expression of fungal virulence factors that result in adherence, invasion, and cell damage [8], which constitute a set of molecular tools that have evolved to overcome the defensive lines of body
We report the identification of enolase 1 as the cell wall protein that has TGase activity, as well as the phenotypic changes produced by inhibition of TGase
Summary
Candida albicans is an opportunistic fungus that is part of the normal microflora commonly found in the human digestive tract and the normal mucosa or skin of healthy individuals. We report here the phenotypic effects produced by the inhibition of transglutaminase enzymatic activity with cystamine, including growth inhibition of yeast cells, induction of autophagy in response to damage caused by cystamine, alteration of the normal yeast division pattern, changes in cell wall, and inhibition of the yeast-to-mycelium transition The latter phenomenon was observed in the C. albicans ATCC 26555 strain. When patients receive prolonged treatments with antibiotics, chemotherapy, or immunosuppressive agents or are in surgical intensive care units, their condition can turn this usually commensal yeast into a pathogen implicated in life-threatening invasive candidiasis [3,4,5,6] Another serious concern that must be considered is the increasing number of cases reporting Candida resistance to antifungal drugs [4]. Other proteins are linked to CWPs through disulfide bonds [14]
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