2020
DOI: 10.1093/genetics/iyaa009
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Genetic contribution to high temperature tolerance in Cryptococcus neoformans

Abstract: 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 gene knockouts were screened for genes essential at 37°C and under conditions that keep calcineurin inactive. Identified 83 candidate strains, potentially sensitive t… Show more

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Cited by 12 publications
(10 citation statements)
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“…Our data indicate the elevated calcineurin signaling in the C. neoformans flc1 Δ mutant leads to aberrant cell wall composition with overaccumulated chitin, a defect that may explain observed hypersensitivity to cell wall damaging agents at 37°C and which is consistent with cell wall integrity defects observed in C. deneoformans flc1 Δ mutant and homologous mutants in other fungi ( 17 , 18 , 21 , 23 ). In addition, C. neoformans mutant lacking Flc1 that was recently identified in a genetic screen, has been shown to exhibit a partial cell separation defect at 37°C, consistent with the aberrant chitin distribution defect reported here ( 55 ).…”
Section: Discussionsupporting
confidence: 86%
“…Our data indicate the elevated calcineurin signaling in the C. neoformans flc1 Δ mutant leads to aberrant cell wall composition with overaccumulated chitin, a defect that may explain observed hypersensitivity to cell wall damaging agents at 37°C and which is consistent with cell wall integrity defects observed in C. deneoformans flc1 Δ mutant and homologous mutants in other fungi ( 17 , 18 , 21 , 23 ). In addition, C. neoformans mutant lacking Flc1 that was recently identified in a genetic screen, has been shown to exhibit a partial cell separation defect at 37°C, consistent with the aberrant chitin distribution defect reported here ( 55 ).…”
Section: Discussionsupporting
confidence: 86%
“…For instance, the ability of C. neoformans to replicate at human body temperature (≥37°C) has been extensively investigated. Many genes have been shown to be essential for thermotolerance ( Perfect, 2006 ; Stempinski et al, 2021 ; Yang et al, 2017 ), including calcineurin which is currently being explored for antifungal drug development ( Gobeil et al, 2021 ). By contrast, the underlying mechanisms or genes that play a role in CO 2 tolerance have yet to be identified.…”
Section: Introductionmentioning
confidence: 99%
“…can grow at 37°C). [20][21][22][23][24] And in warm and dry summers, Cryptococcus concentration in air samples is significantly higher. 25 The effect of relative humidity on Cryptococcus can be explained by dry avian excreta.…”
Section: Discussionmentioning
confidence: 99%