4.6 Review

Replicative Aging in Pathogenic Fungi

Journal

JOURNAL OF FUNGI
Volume 7, Issue 1, Pages -

Publisher

MDPI
DOI: 10.3390/jof7010006

Keywords

aging; fungal pathogen; replicative aging; drug resistance; persister cells; microfluidics; biotinylation; cell isolation; phenotypic variations; high-throughput techniques; fungal pathogen; yeast

Funding

  1. National Institutes of Health [NIH 1R01AI127704-01A1]
  2. US Veterans Affairs Merit Review Award [5I01 BX003741]
  3. NIAID [R01 AI127704]

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Pathogenic yeasts such as Candida albicans, Candida auris, Candida glabrata, and Cryptococcus neoformans undergo replicative aging, leading to phenotypic changes in daughter cells that increase antifungal and antiphagocytic resistance. Studying aging in these yeasts is relevant for understanding virulence, as older cells show key phenotypic variations associated with increased resistance and promote persistence.
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.

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