A Xenobiotic Detoxification Pathway through Transcriptional Regulation in Filamentous Fungi

MBio
Hyunkyu SangGeunhwa Jung

Abstract

Fungi are known to utilize transcriptional regulation of genes that encode efflux transporters to detoxify xenobiotics; however, to date it is unknown how fungi transcriptionally regulate and coordinate different phases of detoxification system (phase I, modification; phase II, conjugation; and phase III, secretion). Here we present evidence of an evolutionary convergence between the fungal and mammalian lineages, whereby xenobiotic detoxification genes (phase I coding for cytochrome P450 monooxygenases [CYP450s] and phase III coding for ATP-binding cassette [ABC] efflux transporters) are transcriptionally regulated by structurally unrelated proteins. Following next-generation RNA sequencing (RNA-seq) analyses of a filamentous fungus, Sclerotinia homoeocarpa, the causal agent of dollar spot on turfgrasses, a multidrug resistant (MDR) field strain was found to overexpress phase I and III genes, coding for CYP450s and ABC transporters for xenobiotic detoxification. Furthermore, there was confirmation of a gain-of-function mutation of the fungus-specific transcription factor S. homoeocarpa XDR1 (ShXDR1), which is responsible for constitutive and induced overexpression of the phase I and III genes, resulting in resistance to multip...Continue Reading

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Citations

Aug 9, 2020·Plant Disease·Xingkai ChengXili Liu
Sep 6, 2018·FEMS Microbiology Letters·Robert GreenGeunhwa Jung
Mar 12, 2020·Mycobiology·Stefanos StravoravdisJonathan P Hulvey
Dec 15, 2020·Current Pharmacology Reports·Joseph L Dempsey, Julia Yue Cui
Mar 7, 2021·Microorganisms·Mengjun Hu, Shuning Chen
Mar 7, 2021·International Journal of Molecular Sciences·Nurhani Mat RazaliKalaivani Nadarajah
Oct 31, 2020·International Journal of Food Microbiology·Marta de Ramón-Carbonell, Paloma Sánchez-Torres
May 20, 2021·Pest Management Science·Chenglin YaoNick X Wang
Aug 28, 2021·Frontiers in Plant Science·Narayan Chandra PaulHyunkyu Sang

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Methods Mentioned

BETA
RNA-seq
immunoprecipitation
ChIP
PCR
genetic modification

Software Mentioned

BLAST
Hisat2
JMP
MEME
Genesis
Blast2GO
BLASTX
Cufflinks
BLASTN

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