Chromosome 5 Monosomy of Candida Albicans Controls Susceptibility to Various Toxic Agents, Including Major Antifungals
Overview
Affiliations
Candida albicans is a prevailing fungal pathogen with a diploid genome that can adapt to environmental stresses by losing or gaining an entire chromosome or a large portion of a chromosome. We have previously found that the loss of one copy of chromosome 5 (Ch5) allows for adaptation to the toxic sugar l-sorbose. l-Sorbose is similar to caspofungin and other antifungals from the echinocandins class, in that it represses synthesis of cell wall glucan in fungi. Here, we extended the study of the phenotypes controlled by Ch5 copy number. We examined 57 strains, either disomic or monosomic for Ch5 and representing five different genetic backgrounds, and found that the monosomy of Ch5 causes elevated levels of chitin and repressed levels of 1,3-β-glucan components of the cell wall, as well as diminished cellular ergosterol. Increased deposition of chitin in the cell wall could be explained, at least partially, by a 2-fold downregulation of CHT2 on the monosomic Ch5 that encodes chitinase and a 1.5-fold upregulation of CHS7 on Ch1 that encodes the protein required for wild-type chitin synthase III activity. Other important outcomes of Ch5 monosomy consist of susceptibility changes to agents representing four major classes of antifungals. Susceptibility to caspofungin increased or decreased and susceptibility to 5-fluorocytosine decreased, whereas susceptibility to fluconazole and amphotericin B increased. Our results suggest that Ch5 monosomy represents an unrecognized C. albicans regulatory strategy that impinges on multiple stress response pathways.
Mannosidases, Dfg5 and Dcw1, Are Required for Cell Wall Integrity and Pathogenesis.
Razmi M, Kim J, Chinnici J, Busarajan S, Vuppalapaty H, Lankipalli D J Fungi (Basel). 2024; 10(8).
PMID: 39194851 PMC: 11355814. DOI: 10.3390/jof10080525.
Ksiezopolska E, Schikora-Tamarit M, Carlos Nunez-Rodriguez J, Gabaldon T Front Cell Infect Microbiol. 2024; 14:1416509.
PMID: 39077431 PMC: 11284152. DOI: 10.3389/fcimb.2024.1416509.
Aneuploidy underlies brefeldin A-induced antifungal drug resistance in .
Zhang Z, Sun L, Fu B, Deng J, Jia C, Miao M Front Cell Infect Microbiol. 2024; 14:1397724.
PMID: 38966251 PMC: 11222406. DOI: 10.3389/fcimb.2024.1397724.
Silva L, Ramos L, Oliveira S, Magalhaes L, Cypriano J, Abreu F J Fungi (Basel). 2023; 9(8).
PMID: 37623630 PMC: 10455776. DOI: 10.3390/jof9080859.
The challenges of the genome-based identification of antifungal resistance in the clinical routine.
Alastruey-Izquierdo A, Martin-Galiano A Front Microbiol. 2023; 14:1134755.
PMID: 37152754 PMC: 10157239. DOI: 10.3389/fmicb.2023.1134755.