Emerging roles of SWI/SNF remodelers in fungal pathogens

Balachandra, Vinutha K; Ghosh, Santanu

doi:10.1007/s00294-021-01219-7

Cited by 3 publications

(1 citation statement)

References 85 publications

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“…The SWI/SNF chromatin remodeling complex has been shown to function in virulence and the transcriptional response to environmental stress in fungal pathogens (reviewed in (Balachandra and Ghosh 2022)). We observed that the acute disruption of SWI/SNF function via conditional depletion of Snf2 had an inhibitory effect on FLC-activated transcription of PDR1 in cells expressing wild-type Pdr1 but not in cells expressing either R376W or D1082G Pdr1 (Figure 5A).…”

Section: Discussionmentioning

confidence: 99%

Overlapping coactivator function is required for transcriptional activation by theCandida glabrataPdr1 transcription factor

Conway,

Simonicova,

Moye-Rowley

2024

Preprint

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Azole resistance in the pathogenic yeastCandida glabratais a serious clinical complication and increasing in frequency. The majority of resistant organisms have been found to contain a substitution mutation in the Zn2Cys6 zinc cluster-containing transcription factor Pdr1. These mutations typically lead to this factor driving high, constitutive expression of target genes like the ATP-binding cassette transporter-encoding geneCDR1. Overexpression of Cdr1 is required for the observed elevated fluconazole resistance exhibited by strains containing one of these hyperactivePDR1alleles. While the identity of hyperactivePDR1alleles has been extensively documented, the mechanisms underlying how these gain-of-function (GOF) forms of Pdr1 lead to elevated target gene transcription are not well understood. We have used a tandem affinity purification (TAP)-tagged form of Pdr1 to identify coactivator proteins that biochemically purify with the wild-type and two different GOF forms of Pdr1. Three coactivator proteins were found to associate with Pdr1: the SWI/SNF complex Snf2 chromatin remodeling protein and two different components of the SAGA complex, Spt7 and Ngg1. We found that deletion mutants lacking eitherSNF2orSPT7exhibited growth defects, even in the absence of fluconazole challenge. To overcome these issues, we employed a conditional degradation system to acutely deplete these coactivators and determined that loss of either coactivator complex, SWI/SNF or SAGA, caused defects in Pdr1-dependent transcription. A double degron strain that could be depleted for both SWI/SNF and SAGA exhibited a profound defect inPDR1autoregulation, revealing that these complexes work together to ensure high level Pdr1-dependent gene transcription.

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Section: Discussionmentioning

confidence: 99%

Overlapping coactivator function is required for transcriptional activation by theCandida glabrataPdr1 transcription factor

Conway,

Simonicova,

Moye-Rowley

2024

Preprint

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Overlapping coactivator function is required for transcriptional activation by the Candida glabrata Pdr1 transcription factor

Conway,

Simonicova,

Moye-Rowley

2024

Genetics

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Azole resistance in the pathogenic yeast Candida glabrata is a serious clinical complication and increasing in frequency. The majority of resistant organisms have been found to contain a substitution mutation in the Zn2Cys6 zinc cluster-containing transcription factor Pdr1. These mutations typically lead to this factor driving high, constitutive expression of target genes like the ATP-binding cassette transporter-encoding gene CDR1. Overexpression of Cdr1 is required for the observed elevated fluconazole resistance exhibited by strains containing one of these hyperactive PDR1 alleles. While the identity of hyperactive PDR1 alleles has been extensively documented, the mechanisms underlying how these gain-of-function (GOF) forms of Pdr1 lead to elevated target gene transcription are not well understood. We have used a tandem affinity purification (TAP)-tagged form of Pdr1 to identify coactivator proteins that biochemically purify with the wild-type and two different GOF forms of Pdr1. Three coactivator proteins were found to associate with Pdr1: the SWI/SNF complex Snf2 chromatin remodeling protein and two different components of the SAGA complex, Spt7 and Ngg1. We found that deletion mutants lacking either SNF2 or SPT7 exhibited growth defects, even in the absence of fluconazole challenge. To overcome these issues, we employed a conditional degradation system to acutely deplete these coactivators and determined that loss of either coactivator complex, SWI/SNF or SAGA, caused defects in Pdr1-dependent transcription. A double degron strain that could be depleted for both SWI/SNF and SAGA exhibited a profound defect in PDR1 autoregulation, revealing that these complexes work together to ensure high level Pdr1-dependent gene transcription.

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Spray-induced gene silencing (SIGS) as a tool for the management of Pine Pitch Canker forest disease

Bocos-Asenjo,

Amin,

Mosquera

et al. 2024

Preprint

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Global change is exacerbating the prevalence of plant diseases caused by pathogenic fungi in forests worldwide. The conventional use of chemical fungicides, which is commonplace in agricultural settings, is not sanctioned for application in forest ecosystems, so novel control strategies are imperative. The promising approach SIGS (Spray-Induced Gene Silencing) involves the external application of specific double-stranded RNA (dsRNA), which can modulate the expression of target genes through environmental RNA interference in eukaryotes. SIGS exhibited notable success in reducing virulence when deployed against some crop fungal pathogens, such as Fusarium graminearum, Botrytis cinerea and Sclerotinia sclerotiorum, among others. However, there is a conspicuous dearth of studies evaluating the applicability of SIGS for managing forest pathogens. This research aimed to determine whether SIGS could be used to control Fusarium circinatum, a widely impactful forest pathogen that causes Pine Pitch Canker disease. To achieve this, we designed and produced though a bacterial synthesis, dsRNA molecules to target fungal essential genes involved to vesicle trafficking (Vps51, DCTN1, and SAC1), signal transduction (Pp2a, Sit4, Ppg1, and Tap42), and cell wall biogenesis (Chs1, Chs2, Chs3b, Gls1) metabolic pathways. We confirmed that F. circinatum is able to uptake externally applied dsRNA, triggering an inhibition of the pathogens virulence. Furthermore, this study pioneers the demonstration that recurrent applications of dsRNAs in SIGS are more effective in protecting plants than single applications. Therefore, SIGS emerges as an effective and sustainable approach for managing plant pathogens, showcasing its efficacy in controlling a globally significant forest pathogen subject to quarantine measures.

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Emerging roles of SWI/SNF remodelers in fungal pathogens

Cited by 3 publications

References 85 publications

Overlapping coactivator function is required for transcriptional activation by theCandida glabrataPdr1 transcription factor

Overlapping coactivator function is required for transcriptional activation by theCandida glabrataPdr1 transcription factor

Overlapping coactivator function is required for transcriptional activation by the Candida glabrata Pdr1 transcription factor

Spray-induced gene silencing (SIGS) as a tool for the management of Pine Pitch Canker forest disease

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