Suppressed Protein Translation Caused by MSP-8 Deficiency Determines Fungal Multidrug Resistance with Fitness Cost.

Antifungal resistance, particularly the rise of multidrug-resistance strains, poses a significant public health threat. In this study, the study identifies a novel multidrug-resistance gene, msp-8, encoding a helicase, through experimental evolution with Neurospora crassa as a model. Deletion of msp-8 conferred multidrug resistance in N.

PWWP domain-containing protein Crf4-3 specifically modulates fungal azole susceptibility by regulating sterol C-14 demethylase ERG11.

The widespread use of azole antifungals in agriculture and clinical settings has led to serious drug resistance. Overexpression of the azole drug target 14α-demethylase ERG11 (CYP51) is the most common fungal resistance mechanism. However, the presence of additional regulatory proteins in the transcriptional response of is not yet fully elucidated.

Long-term stability of reactor microbiome through bioaugmentation with Alcaligenes aquatilis AS1 promotes nitrogen removal of piggery wastewater.

Bioaugmentation is considered as an attractive method for nitrogen removal in water treatment, but its effectiveness in actual high-strength piggery wastewater has not been adequately verified and the mechanism of bioaugmentation in actual wastewater treatment system is not very clear especially from the perspectives of microbial communities and functional genes. This study investigated the mechanisms of a heterotrophic nitrifying-aerobic denitrifying strain Alcaligenes aquatilis AS1 in the bioaugmentation of continuous biological nitrogen removal of actual piggery wastewater at laboratory scale. The addition of strain AS1 significantly improved the nitrogen removal efficiency (more than 95% of NH-N and 75% of TN were removed) and raised the activated sludge resistance to shock loading.

Improving suppressive activity of compost on phytopathogenic microbes by inoculation of antagonistic microorganisms for secondary fermentation.

Antimicrobial activity contributes to plant disease control property of composts but its source is still not clear. From composting cow manure during secondary fermentation, 50 microbial strains with antifungal activity were isolated and identified. Two bacterial strains Bacillus mojavensis B282 and Pseudomonas aeruginosa F288, antagonistic against both phytopathogenic fungi and bacteria, were respectively used as the inoculum of compost for secondary fermentation.

Characterization of Alcaligenes aquatilis as a novel member of heterotrophic nitrifier-aerobic denitrifier and its performance in treating piggery wastewater.

A novel strain AS1 with heterotrophic nitrifying-aerobic denitrifying capacity in the species of Alcaligenes aquatilis was isolated from the aerobic activated sludge. It showed a great capability of ammonia removal, and the aerobic metabolic pathways to yield gaseous-nitrogen by hydroxylamine oxidation and nitrite denitrification were proposed. AS1 could efficiently remove ammonia under a wide range of environmental conditions, including the ratio of chemical oxygen demand to total nitrogen: 15-30, pH: 6-10, NaCl: 0-60 g/L, shaking speed of 0-180 rpm, and succinate, acetate, or citrate as carbon source.

Experimental Evolution of Multidrug Resistance in under Antifungal Azole Stress.

Multidrug resistance, defined as the resistance to multiple drugs in different categories, has been an increasing serious problem. Limited antifungal drugs and the rapid emergence of antifungal resistance prompt a thorough understanding of how the occurrence of multidrug resistance develops and which mechanisms are involved. In this study, experimental evolution was performed under single-azole-drug stress with the model filamentous fungus .

Coordinated Regulation of Membrane Homeostasis and Drug Accumulation by Novel Kinase STK-17 in Response to Antifungal Azole Treatment.

The emergence of antifungal resistance, especially to the most widely used azole class of ergosterol biosynthesis inhibitors, makes fungal infections difficult to treat in clinics and agriculture. When exposed to azoles, fungi can make adaptive responses to alleviate azole toxicity and produce azole tolerance. However, except for azole efflux pumps and ergosterol biosynthesis genes, the role of most azole responsive genes in azole resistance is unknown.

Coordinated Regulation of Protoperithecium Development by MAP Kinases MAK-1 and MAK-2 in .

Mitogen-activated protein (MAP) kinase pathways function as signaling hubs that are integral for many essential cellular processes, including sexual development. The molecular mechanisms and cross-talk between PR and CWI MAP kinase pathways have been extensively studied during asexual development. However, if these can be extended to sexual development remains elusive.

Candicidin Isomer Production Is Essential for Biocontrol of Cucumber Rot by Streptomyces albidoflavus W68.

Diseases caused by soilborne fungal pathogens result in significant crop yield losses and quality reduction. strain W68 is effective in controlling several soilborne fungal diseases. To identify antifungal substances critical for biocontrol activity of W68, the genome of W68 was sequenced and a linear chromosome of 6.

Fungal Zn(II)Cys Transcription Factor ADS-1 Regulates Drug Efflux and Ergosterol Metabolism under Antifungal Azole Stress.

Antifungal azoles are the most widely used antifungal drugs in clinical and agricultural practice. Fungi can mount adaptive responses to azole stress by modifying the transcript levels of many genes, and the responsive mechanisms to azoles are the basis for fungi to develop azole resistance. In this study, we identified a new Zn(II)Cys transcription factor, ADS-1, with a positive regulatory function in transcriptional responses to azole stress in the model filamentous fungal species Under ketoconazole (KTC) stress, the transcript level was significantly increased in Deletion of increased susceptibility to different azoles, while its overexpression increased resistance to these azoles.

The Zn(II)2Cys6-Type Transcription Factor ADA-6 Regulates Conidiation, Sexual Development, and Oxidative Stress Response in .

Conidiation and sexual development are critical for reproduction, dispersal and better-adapted survival in many filamentous fungi. The gene encodes a Zn(II)2Cys6-type transcription factor, whose deletion resulted in reduced conidial production and female sterility. In this study, we confirmed the positive contribution of to conidiation and sexual development by detailed phenotypic characterization of its deletion mutant and the complemented mutant.

Transcription factor CCG-8 plays a pivotal role in azole adaptive responses of Neurospora crassa by regulating intracellular azole accumulation.

Azoles are the most widely used antifungals for controlling fungal infections in clinic and agriculture. Fungi can adapt to azole stress by rapidly activating the transcription of a number of genes, and some of these genes can elevate resistance to azoles. We had reported the transcription factor CCG-8 as a new regulator in the adaptation to antifungal azole stress in Neurospora crassa and Fusarium verticillioides.

Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles.

Fungi transcriptionally upregulate expression of azole efflux pumps and ergosterol biosynthesis pathway genes when exposed to antifungal agents that target ergosterol biosynthesis. To date, these transcriptional responses have been shown to be dependent on the presence of the azoles and/or depletion of ergosterol. Using an inducible promoter to regulate , which encodes the major azole target, sterol 14α-demethylase, we were able to demonstrate that the CDR4 azole efflux pump can be transcriptionally activated by ergosterol biosynthesis inhibition even in the absence of azoles.

Antisense transcription licenses nascent transcripts to mediate transcriptional gene silencing.

In eukaryotes, antisense transcription can regulate sense transcription by induction of epigenetic modifications. We showed previously that antisense transcription triggers Dicer-independent siRNA (disiRNA) production and disiRNA locus DNA methylation (DLDM) in Neurospora crassa Here we show that the conserved exonuclease ERI-1 (enhanced RNAi-1) is a critical component in this process. Antisense transcription and ERI-1 binding to target RNAs are necessary and sufficient to trigger DLDM.

The Hsp90 Co-chaperones Sti1, Aha1, and P23 Regulate Adaptive Responses to Antifungal Azoles.

Heat Shock Protein 90 (Hsp90) is essential for tumor progression in humans and drug resistance in fungi. However, the roles of its many co-chaperones in antifungal resistance are unknown. In this study, by susceptibility test of mutants lacking each of 18 Hsp90/Calcineurin system member genes (including 8 Hsp90 co-chaperone genes) to antifungal drugs and other stresses, we demonstrate that the Hsp90 co-chaperones Sti1 (Hop1 in yeast), Aha1, and P23 (Sba1 in yeast) were required for the basal resistance to antifungal azoles and heat stress.

Fruiting Body Formation in Volvariella volvacea Can Occur Independently of Its MAT-A-Controlled Bipolar Mating System, Enabling Homothallic and Heterothallic Life Cycles.

Volvariella volvacea is an important crop in Southeast Asia, but erratic fruiting presents a serious challenge for its production and breeding. Efforts to explain inconsistent fruiting have been complicated by the multinucleate nature, typical lack of clamp connections, and an incompletely identified sexual reproductive system. In this study, we addressed the life cycle of V.

De-repression of CSP-1 activates adaptive responses to antifungal azoles.

Antifungal azoles are the major drugs that are used to treat fungal infections. This study found that in response to antifungal azole stress, Neurospora crassa could activate the transcriptional responses of many genes and increase azole resistance by reducing the level of conidial separation 1 (CSP-1), a global transcription repressor, at azole-responsive genes. The expression of csp-1 was directly activated by the transcription factors WC-1 and WC-2.

Transcription factor ADS-4 regulates adaptive responses and resistance to antifungal azole stress.

Azoles are commonly used as antifungal drugs or pesticides to control fungal infections in medicine and agriculture. Fungi adapt to azole stress by rapidly activating the transcription of a number of genes, and transcriptional increases in some azole-responsive genes can elevate azole resistance. The regulatory mechanisms that control transcriptional responses to azole stress in filamentous fungi are not well understood.

Specific adaptation of Ustilaginoidea virens in occupying host florets revealed by comparative and functional genomics.

Ustilaginoidea virens (Cooke) Takah is an ascomycetous fungus that causes rice false smut, a devastating emerging disease worldwide. Here we report a 39.4 Mb draft genome sequence of U.

Transcription factor CCG-8 as a new regulator in the adaptation to antifungal azole stress.

Antifungal azoles are widely used for controlling fungal infections. Fungi are able to change the expression of many genes when they adapt to azole stress, and increased expression of some of these genes can elevate resistance to azoles. However, the regulatory mechanisms behind transcriptional adaption to azoles in filamentous fungi are poorly understood.

Correction: Composition and Expression of Genes Encoding Carbohydrate-Active Enzymes in the Straw-Degrading Mushroom .

[This corrects the article on p. e58780 in vol. 8.

Genetic diversity and population structure of rice pathogen Ustilaginoidea virens in China.

Rice false smut caused by the fungal pathogen Ustilaginoidea virens is becoming a destructive disease throughout major rice-growing countries. Information about its genetic diversity and population structure is essential for rice breeding and efficient control of the disease. This study compared the genome sequences of two U.

Sterol C-22 Desaturase ERG5 Mediates the Sensitivity to Antifungal Azoles in Neurospora crassa and Fusarium verticillioides.

Antifungal azoles inhibit ergosterol biosynthesis by interfering with lanosterol 14α-demethylase. In this study, seven upregulated and four downregulated ergosterol biosynthesis genes in response to ketoconazole treatment were identified in Neurospora crassa. Azole sensitivity test of knockout mutants for six ketoconazole-upregulated genes in ergosterol biosynthesis revealed that deletion of only sterol C-22 desaturase ERG5 altered sensitivity to azoles: the erg5 mutant was hypersensitive to azoles but had no obvious defects in growth and development.

PyrG is required for maintaining stable cellular uracil level and normal sporulation pattern under excess uracil stress in Aspergillus nidulans.

Tight control of the intracellular uracil level is believed to be important to reduce the occurrence of uracil incorporation into DNA. The pyrG gene of Aspergillus nidulans encodes orotidine 5'-phosphate decarboxylase, which catalyzes the conversion of orotidine monophosphate (OMP) to uridine monophosphate (UMP). In this study, we found that pyrG is critical for maintaining uracil at a low concentration in A.