Abstract
Candida albicans, Candida auris, Candida glabrata, and Cryptococcus neoformans are pathogenic yeasts which can cause systemic infections in immune-compromised as well as immune-competent individuals. These yeasts undergo replicative aging analogous to a process first described in the nonpathogenic yeast Saccharomyces cerevisiae. The hallmark of replicative aging is the asymmetric cell division of mother yeast cells that leads to the production of a phenotypically distinct daughter cell. Several techniques to study aging that have been pioneered in S. cerevisiae have been adapted to study aging in other pathogenic yeasts. The studies indicate that aging is relevant for virulence in pathogenic fungi. As the mother yeast cell progressively ages, every ensuing asymmetric cell division leads to striking phenotypic changes, which results in increased antifungal and antiphagocytic resistance. This review summarizes the various techniques that are used to study replicative aging in pathogenic fungi along with their limitations. Additionally, the review summarizes some key phenotypic variations that have been identified and are associated with changes in virulence or resistance and thus promote persistence of older cells.
Highlights
Most fungal pathogens cause subacute or chronic infections
A mother cell can only produce a finite number of buds during mitotic division, and the total number of buds that a mother cell produces before it stops dividing and dies is the designated replicative life span (RLS) of that yeast cell
There is a set of published data that indicates that older mother cells of several pathogenic fungi, including Candida glabrata, Candida auris, Candida albicans, and Cryptococcus neoformans, exhibit enhanced resilience to antifungals and oxidative stress, J
Summary
Most fungal pathogens cause subacute or chronic infections. One major challenge in designing effective antifungal drug therapy is a knowledge gap regarding the impact of microbial microevolution in the host during chronic infection on antifungal resistance of the respective fungal population. There is a set of published data that indicates that older mother cells of several pathogenic fungi, including Candida glabrata, Candida auris, Candida albicans, and Cryptococcus neoformans, exhibit enhanced resilience to antifungals and oxidative stress, J. There is a set of published data that indicates that older mother cells of several pathogenic fungi, including Candida glabrata, Candida auris, Candida albicans, and Cryptococcus neoformans, exhibit enhanced resilience to antifungals and oxidative stress, which could wphoitcehnctoiaullldy gpiovteenthtieamllyagnivaedtvhaenmtaagne aindvthaenthaogsetienntvhierohnomsteenntv. This method creates a discontinuity in the analysis, as at the end of the day the culture plates are refrigerated to slow down the replication time This can cause unnecessary stress on the cells resulting in erroneous RLS determination. This makes identifying daughter cells difficult, causing erroneous RLS analysis
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