Judith BERMAN – Tel Aviv University – Israel
Rapid responses to acute stresses are essential for stress survival and adaptation. An excellent microbial model for this process is the rapid emergence of drug resistance in fungal pathogens. Fungi can adapt and survive drug concentrations that inhibit the growth of progenitor cells. They often do so via large effect size mutations involving whole chromosomes, chromosome arms as well as some point mutations, in a manner similar to cancer cells responding to chemotherapy drugs. Specifically, they undergo ploidy switches, alter chromosome copy number (become aneuploid) and undergo frequent loss of heterozygosity, via recombination and chromosome mis-segregation. Drug exposure can drive these changes, via the formation of trimeras (three connected cells with four nuclei) that produce tetraploid progeny. These tetraploids retain two mitotic spindles and frequently mis-segregate chromosomes to yield aneuploids. Thus, aneuploidy is induced by drug and some genes present in altered copy number on those chromosomes can facilitate survival in the same drug. Subsequently, the proportion of adapted cells is enriched in the population. Accordingly, aneuploid formation is a mechanism enabling rapid and transient generation of diversity upon which selection can act.
Site web du laboratoire : http://www6.tau.ac.il/berman/
Contact : Christophe d’Enfert (firstname.lastname@example.org)