Gene Expression of Pneumocystis murina after Treatment with Anidulafungin Results in Strong Signals for Sexual Reproduction, Cell Wall Integrity, and Cell Cycle Arrest, Indicating a Requirement for Ascus Formation for Proliferation

Antimicrobial Agents and Chemotherapy
Melanie T CushionAleksey Porollo

Abstract

The echinocandins are a class of antifungal agents that target β-1,3-d-glucan (BG) biosynthesis. In the ascigerous Pneumocystis species, treatment with these drugs depletes the ascus life cycle stage, which contains BG, but large numbers of forms which do not express BG remain in the infected lungs. In the present study, the gene expression profiles of Pneumocystis murina were compared between infected, untreated mice and mice treated with anidulafungin for 2 weeks to understand the metabolism of the persisting forms. Almost 80 genes were significantly up- or downregulated. Like other fungi exposed to echinocandins, genes associated with sexual replication, cell wall integrity, cell cycle arrest, and stress comprised the strongest upregulated signals in P. murina from the treated mice. The upregulation of the P. murina β-1,3-d-glucan endohydrolase and endo-1,3-glucanase was notable and may explain the disappearance of the existing asci in the lungs of treated mice since both enzymes can degrade BG. The biochemical measurement of BG in the lungs of treated mice and fluorescence microscopy with an anti-BG antibody supported the loss of BG. Downregulated signals included genes involved in cell replication, genome stability, and ri...Continue Reading

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Citations

May 4, 2018·The Journal of Eukaryotic Microbiology·Melanie T CushionLouis M Weiss
Dec 7, 2018·PLoS Pathogens·Philippe M Hauser, Melanie T Cushion
Sep 25, 2019·Antimicrobial Agents and Chemotherapy·Gilles Nevez, Solène Le Gal
May 5, 2020·Journal of Biomedical Materials Research. Part a·Noel Vera-GonzálezAnita Shukla
Jul 29, 2018·Antimicrobial Agents and Chemotherapy·Gilles NevezSolène Le Gal
Jan 25, 2021·Revista iberoamericana de micología·Mercedes RomeroGabriela Santiso
Jun 8, 2021·Frontiers in Microbiology·Melanie T CushionAleksey Porollo
Jun 17, 2021·Microbiology and Molecular Biology Reviews : MMBR·Philippe M Hauser

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Datasets Mentioned

BETA
EMR09078.1
EMR11067.1
EMR08305.1

Methods Mentioned

BETA
RNA-seq
environmental stress
glycosylation
PCR
chip

Software Mentioned

AltAnalyze
GraphPad Instat
Kallisto
BLASTp suite
SmartBLAST
GraphPad
PrepX PolyA script
Depletion script
Ribo

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