title: Genetic Screens for Determination of Mechanism of Action.
abstract: The search for new antifungal drugs and cell targets continues. During the discovery process, mechanism-of-action (MOA) studies are critical to the continued progress of the compound through the pipeline. There are many approaches that can be utilized in understanding the MOA. One of these approaches is a genetic screen utilizing the availability of Saccharomyces cerevisiae mutant libraries. Both null and heterozygous library mutants covering the entire genome of this model yeast are available. The desired phenotype when screening the new compound is either resistance (null mutants) or haploinsufficiency or loss of fitness (heterozygote mutants). Both types of mutants can be clustered by software into common targets that provide clues as to a pathway or other cell process. Below, methods are described for genetic screens.
authors.affiliation: Department of Pathology, GU-MedStar Hospital, Georgetown University Medical Center, Washington DC, USA. francoise.gay-andrieu@biomerieux.com.
authors.forename: Françoise
authors.initials: F
authors.lastname: Gay-Andrieu
authors.affiliation: Department of Pathology, GU-MedStar Hospital, Georgetown University Medical Center, Washington DC, USA. deepu.alex@gmail.com.
authors.forename: Deepu
authors.initials: D
authors.lastname: Alex
authors.affiliation: Department of Microbiology & Immunology, Georgetown University Medical Center, Washington DC, 20057, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Calderone
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D025141:Drug Resistance, Fungal; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005838:Genotype; D057895:Haploinsufficiency; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000935:Antifungal Agents
keywords: Genetic screen; Haploinsufficiency; MIC; MOA; Susceptibility