Genetic contribution to high temperature tolerance in Cryptococcus neoformans.
The human fungal pathogen Cryptococcus neoformans relies on a complex signaling network for the adaptation and survival at the host temperature. Protein phosphatase calcineurin is central to proliferation at 37°C but its exact contributions remain ill-defined. To better define genetic contributions...
| Publicado en: | Genetics Vol. 217; no. 1; pp. 1 - 16 |
|---|---|
| Autores principales: | , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Oxford University Press / USA
Jan2021
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=149445244&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 149445244 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00166731 GNT jtl: Genetics issn: 00166731 maglogo: N pubinfo: dt: Jan2021 vid: 217 iid: 1 pid: 622 pub: Oxford University Press / USA artinfo: ui: 149445244 149445244 149445244 10.1093/genetics/iyaa009 149445244 ppf: 1 ppct: 15 formats: tig: atl: Genetic contribution to high temperature tolerance in Cryptococcus neoformans. aug: au: Stempinski, Piotr R. Zielinski, Jessica M. Dbouk, Nadir H. Huey, Elizabeth S. McCormack, Ellen C. Rubin, Alexander M. Chandrasekaran, Srikripa Kozubowski, Lukasz affil: Department of Genetics & Biochemistry, Eukaryotic Pathogens Innovation Center (EPIC), Clemson University, Clemson, SC 29634, USA sug: subj: Temperature Genetics Cryptococcus Physiology Genes Immunosuppressive Agents Genetic Screening Mutation Proteins Cell Physiology Cell Proliferation ab: The human fungal pathogen Cryptococcus neoformans relies on a complex signaling network for the adaptation and survival at the host temperature. Protein phosphatase calcineurin is central to proliferation at 37°C but its exact contributions remain ill-defined. To better define genetic contributions to the C. neoformans temperature tolerance, 4031 geneknockouts were screened for genes essential at 37°C and under conditions that keep calcineurin inactive. Identified 83 candidate strains, potentially sensitive to 37°C, were subsequently subject to technologically simple yet robust assay, in which cells are exposed to a temperature gradient. This has resulted inidentification of 46 genes contributingto the maximum temperature at which C. neoformans can proliferate (Tmax). The 46 mutants, characterized by a range of Tmax on drug-free media, were further assessed for Tmax under conditions that inhibit calcineurin, which led to identification of several previously uncharacterized knockouts exhibiting synthetic interaction with the inhibition of calc neurin. A mutant that lacked septin Cdc11 was among those with the lowest Tmax and failed to proliferate in the absence of calcineurin activity. To further define connections with calcineurin and the role for septins in high temperaturegrowth, the 46 mutants were tested for cell morphology at 37°C and growth in the presence of agents disrupting cell wall and cell membrane. Mutants sensitive to calcineurin inhibition were tested for synthetic lethal interaction with deletion of the septin-encoding CDC12 and the localization of the septin Cdc3-mCherry. The analysis described here pointed to previously uncharacterized genes that were missed in standard growth assays indicating that the temperature gradient assay is a valuable complementary tool for elucidating the genetic basis of temperature range at which microorganisms proliferate. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|