Fluconazole Induces Aneuploidy, Sowing the Seeds of Its Own Failure

http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001816

Fluconazole, in the azole class, is the most widely used antifungal drug worldwide. Fluconazole is highly effective, but resistance is becoming increasingly common.
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Fluconazole inhibits the growth of fungal membranes without killing them, which likely explains the results seen here: treatment disrupted the normal coordination of membrane and nuclear events, leaving chromosomes to separate without a new cell to separate into, forming tetraploids. Treatment means that some tetraploids will become aneuploid, and some aneuploids will be overloaded with drug-resistance genes.

The discovery of this phenomenon is troubling, since it means that treatment sows the seeds of its own failure. Since the yeast are inhibited but not killed, they remain in place even after successful treatment, and longer treatment doesn't eradicate the resistant cells. But understanding the origin of that resistance may allow the design of drugs that can either overcome it or exploit a pathway that avoids it.