Chromosome Instability & Drug Resistance

Candida albicans

Candida albicans is a unicellular budding fungus that forms part of normal gut or genitalia microflora. In immunocompromized humans, however, C. albicans becomes an important opportunistic pathogen that can cause mortality. C. albicans is unique among other fungal pathogens by having an ability to infect divers sites of human body, including skin, nails, mucosal surfaces, as well as any other tissues or inner organs. In the laboratory, this fungus demonstrates an impressive ability to flourish under extreme pH and temperatures, as well as in other extreme environments. C. albicans possesses an acute ability to counter act the environmental stresses and to mount adequate phenotypic responses.

Since 1935, scientists reported spontaneously occurring colonies of C. albicans that derived from regular smooth colonies and had various altered colony forms, as well as multiple phenotypic changes. We demonstrated that various spontaneous chromosomal alterations are responsible for alterations of colony appearances. Importantly, we also showed that chromosomal alterations contribute to the diversity of phenotypes in population of cells, including utilization of nutrients.

We made the remarkable discovery that C. albicans evolved an unusual mechanism of survival in adverse environments that cause lethality or inhibit growth. This naturally diploid microbe adapts to a specific environment by losing or gaining an entire specific chromosome or a large portion of a specific chromosome. For example, survival on the medium containing the antifungal drug caspofungin or the toxic sugar L-sorbose, which kills C. albicans in a fashion similar to caspofungin, involves the loss of one copy of chromosome 5 (Ch5).