Eradication of broad-spectrum multi-drug fungal pathogens through photoinactivation of a detoxifying enzyme (Conference Presentation)

2020 ◽  
Author(s):  
Pu-Ting Dong ◽  
Zeina Dagher ◽  
Yuewei Zhan ◽  
Jie Hui ◽  
Michael K. Mansour ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Fungal Pathogens ◽  
Detoxifying Enzyme

scholarly journals Overexpression of NPR1 in Brassica juncea Confers Broad Spectrum Resistance to Fungal Pathogens

2017 ◽  
Vol 8 ◽  
Author(s):  
Sajad Ali ◽  
Zahoor A. Mir ◽  
Anshika Tyagi ◽  
Hailay Mehari ◽  
Rajendra P. Meena ◽  
...  
Keyword(s):  
Brassica Juncea ◽  
Broad Spectrum ◽  
Fungal Pathogens ◽  
Broad Spectrum Resistance

scholarly journals Characterization of Volatile Organic Compounds Emitted from Endophytic Burkholderia cenocepacia ETR-B22 by SPME-GC-MS and Their Inhibitory Activity against Various Plant Fungal Pathogens

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3765
Author(s):  
Jian-Hua Chen ◽  
Wei Xiang ◽  
Ke-Xin Cao ◽  
Xuan Lu ◽  
Shao-Chang Yao ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Volatile Organic Compounds ◽  
Organic Compounds ◽  
Broad Spectrum ◽  
Fungal Pathogens ◽  
Control Plant ◽  
Burkholderia Cenocepacia ◽  
Nonanoic Acid ◽  
Antagonistic Microorganisms ◽  
Volatile Organic

The use of antagonistic microorganisms and their volatile organic compounds (VOCs) to control plant fungal pathogens is an eco-friendly and promising substitute for chemical fungicides. In this work, endophytic bacterium ETR-B22, isolated from the root of Sophora tonkinensis Gagnep., was found to exhibit strong antagonistic activity against 12 fungal pathogens found in agriculture. Strain ETR-B22 was identified as Burkholderia cenocepacia based on 16S rRNA and recA sequences. We evaluated the antifungal activity of VOCs emitted by ETR-B22. The VOCs from strain ETR-B22 also showed broad-spectrum antifungal activity against 12 fungal pathogens. The composition of the volatile profiles was analyzed based on headspace solid phase microextraction (HS-SPME) gas chromatography coupled to mass spectrometry (GC-MS). Different extraction strategies for the SPME process significantly affected the extraction efficiency of the VOCs. Thirty-two different VOCs were identified. Among the VOC of ETR-B22, dimethyl trisulfide, indole, methyl anthranilate, methyl salicylate, methyl benzoate, benzyl propionate, benzyl acetate, 3,5-di-tert-butylphenol, allyl benzyl ether and nonanoic acid showed broad-spectrum antifungal activity, and are key inhibitory compounds produced by strain ETR-B22 against various fungal pathogens. Our results suggest that the endophytic strain ETR-B22 and its VOCs have high potential for use as biological controls of plant fungal pathogens.

scholarly journals Toxoflavin Produced byBurkholderia gladiolifromLycoris aureaIs a New Broad-Spectrum Fungicide

2019 ◽  
Vol 85 (9) ◽  
Author(s):  
Xiaodan Li ◽  
Yikui Li ◽  
Ren Wang ◽  
Qizhi Wang ◽  
Ling Lu
Keyword(s):  
Antifungal Activity ◽  
Broad Spectrum ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Endophytic Bacterium ◽  
Content Type ◽  
Burkholderia Gladioli ◽  
Lycoris Aurea ◽  
Resistant Mutants

ABSTRACTFungal infections not only cause extensive agricultural damage but also result in serious diseases in the immunodeficient populations of human beings. Moreover, the increasing emergence of drug resistance has led to a decrease in the efficacy of current antifungals. Thus, screening of new antifungal agents is imperative in the fight against antifungal drug resistance. In this study, we show that an endophytic bacterium,Burkholderia gladioliHDXY-02, isolated from the medicinal plantLycoris aurea, showed broad-spectrum antifungal activity against plant and human fungal pathogens. An antifungal ability assay indicated that the bioactive component was produced from strain HDXY-02 having an extracellular secreted component with a molecular weight lower than 1,000 Da. In addition, we found that this new antifungal could be produced effectively by liquid fermentation of HDXY-02. Furthermore, the purified component contributing to the antifungal activity was identified to be toxoflavin, a yellow compound possessing a pyrimido[5,4-e][1,2,4]triazine ring.In vitrobioactivity studies demonstrated that purified toxoflavin fromB. gladioliHDXY-02 cultures had a significant antifungal activity against the human fungal pathogenAspergillus fumigatus, resulting in abolished germination of conidia. More importantly, the growth inhibition by toxoflavin was observed in both wild-type and drug-resistant mutants (cyp51Aand non-cyp51A) ofA. fumigatus. Finally, an optimized protocol for the large-scale production of toxoflavin (1,533 mg/liter) has been developed. Taken together, our findings provide a promising biosynthetic resource for producing a new antifungal reagent, toxoflavin, from isolates of the endophytic bacteriumB. gladioli.IMPORTANCEHuman fungal infections are a growing problem associated with increased morbidity and mortality. Moreover, a growing number of antifungal-resistant fungal isolates have been reported over the past decade. Thus, the need for novel antifungal agents is imperative. In this study, we show that an endophytic bacterium,Burkholderia gladioli, isolated from the medicinal plantLycoris aurea, is able to abundantly secrete a compound, toxoflavin, which has a strong fungicidal activity not only against plant fungal pathogens but also against human fungal pathogensAspergillus fumigatusandCandida albicans,Cryptococcus neoformans, and the model filamentous fungusAspergillus nidulans. More importantly, toxoflavin also displays an efficacious inhibitory effect against azole antifungal-resistant mutants ofA. fumigatus. Consequently, our findings provide a promising approach to abundantly produce toxoflavin, which has novel broad-spectrum antifungal activity, especially against those currently problematic drug-resistant isolates.

Benzimidazole tethered pyrrolo[3,4-b]quinoline with broad-spectrum activity against fungal pathogens

2019 ◽  
Vol 29 (5) ◽  
pp. 729-733 ◽  
Author(s):  
Pedro Villa ◽  
Natarajan Arumugam ◽  
Abdulrahman I. Almansour ◽  
Raju Suresh Kumar ◽  
S.M. Mahalingam ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Fungal Pathogens ◽  
Spectrum Activity ◽  
Broad Spectrum Activity

scholarly journals Conserved Fungal Genes as Potential Targets for Broad-Spectrum Antifungal Drug Discovery

2006 ◽  
Vol 5 (4) ◽  
pp. 638-649 ◽  
Author(s):  
Mengping Liu ◽  
Matthew D. Healy ◽  
Brian A. Dougherty ◽  
Kim M. Esposito ◽  
Trina C. Maurice ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Fungal Pathogens ◽  
Antifungal Drugs ◽  
Genome Comparison ◽  
Genome Wide ◽  
Conditional Mutant ◽  
A Genome ◽  
Conserved Genes ◽  
Wide Scale ◽  
Fungal Genes

ABSTRACT The discovery of novel classes of antifungal drugs depends to a certain extent on the identification of new, unexplored targets that are essential for growth of fungal pathogens. Likewise, the broad-spectrum capacity of future antifungals requires the target gene(s) to be conserved among key fungal pathogens. Using a genome comparison (or concordance) tool, we identified 240 conserved genes as candidates for potential antifungal targets in 10 fungal genomes. To facilitate the identification of essential genes in Candida albicans, we developed a repressible C. albicans MET3 (CaMET3) promoter system capable of evaluating gene essentiality on a genome-wide scale. The CaMET3 promoter was found to be highly amenable to controlled gene expression, a prerequisite for use in target-based whole-cell screening. When the expression of the known antifungal target C. albicans ERG1 was reduced via down-regulation of the CaMET3 promoter, the CaERG1 conditional mutant strain became hypersensitive, specifically to its inhibitor, terbinafine. Furthermore, parallel screening against a small compound library using the CaERG1 conditional mutant under normal and repressed conditions uncovered several hypersensitive compound hits. This work therefore demonstrates a streamlined process for proceeding from selection and validation of candidate antifungal targets to screening for specific inhibitors.

scholarly journals Hexadecylphosphocholine (Miltefosine) Has Broad-Spectrum Fungicidal Activity and Is Efficacious in a Mouse Model of Cryptococcosis

2006 ◽  
Vol 50 (2) ◽  
pp. 414-421 ◽  
Author(s):  
Fred Widmer ◽  
Lesley C. Wright ◽  
Daniel Obando ◽  
Rosemary Handke ◽  
Ranjini Ganendren ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Mouse Model ◽  
Broad Spectrum ◽  
Fungal Pathogens ◽  
Inhibitory Effect ◽  
Fungal Virulence ◽  
Antifungal Effect ◽  
Pancreatic Phospholipase ◽  
Scedosporium Prolificans

ABSTRACT The alkyl phosphocholine drug miltefosine is structurally similar to natural substrates of the fungal virulence determinant phospholipase B1 (PLB1), which is a potential drug target. We determined the MICs of miltefosine against key fungal pathogens, correlated antifungal activity with inhibition of the PLB1 activities (PLB, lysophospholipase [LPL], and lysophospholipase-transacylase [LPTA]), and investigated its efficacy in a mouse model of disseminated cryptococcosis. Miltefosine inhibited secreted cryptococcal LPTA activity by 35% at the subhemolytic concentration of 25 μM (10.2 μg/ml) and was inactive against mammalian pancreatic phospholipase A2 (PLA2). At 250 μM, cytosolic PLB, LPL, and LPTA activities were inhibited by 25%, 51%, and 77%, respectively. The MICs at which 90% of isolates were inhibited (MIC90s) against Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, Cryptococcus gattii, Aspergillus fumigatus, Fusarium solani, Scedosporium prolificans, and Scedosporium apiospermum were 2 to 4 μg/ml. The MICs of miltefosine against Candida tropicalis (n = 8) were 2 to 4 μg/ml, those against Aspergillus terreus and Candida parapsilosis were 8 μg/ml (MIC90), and those against Aspergillus flavus (n = 8) were 2 to 16 μg/ml. Miltefosine was fungicidal for C. neoformans, with rates of killing of 2 log units within 4 h at 7.0 μM (2.8 μg/ml). Miltefosine given orally to mice on days 1 to 5 after intravenous infection with C. neoformans delayed the development of illness and mortality and significantly reduced the brain cryptococcal burden. We conclude that miltefosine has broad-spectrum antifungal activity and is active in vivo in a mouse model of disseminated cryptococcosis. The relatively small inhibitory effect on PLB1 enzyme activities at concentrations exceeding the MIC by 2 to 20 times suggests that PLB1 inhibition is not the only mechanism of the antifungal effect.

scholarly journals Biological control of collar rot disease with broad-spectrum antifungal bacteria associated with groundnut

2005 ◽  
Vol 51 (2) ◽  
pp. 123-132 ◽  
Author(s):  
G Krishna Kishore ◽  
S Pande ◽  
A R Podile
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Broad Spectrum ◽  
Fungal Pathogens ◽  
Crown Rot ◽  
Cercospora Arachidicola ◽  
Collar Rot ◽  
Rhizoctonia Bataticola ◽  
Culture Filtrates ◽  
Necrotrophic Fungi ◽  
Biotrophic Fungi

Bacteria associated with 6 habitats of groundnut were evaluated for their broad-spectrum antifungal activity and suppression of collar rot (Aspergillus niger) of groundnut. Three hundred and ninety-three strains were tested against 8 fungal pathogens of groundnut including 5 necrotrophic fungi, Aspergillus flavus, A. niger, Rhizoctonia bataticola, Rhizoctonia solani, and Sclerotium rolfsii, and 3 biotrophic fungi, Cercospora arachidicola, Phaeoisariopsis personata, and Puccinia arachidis. Pseudomonas sp. GRS 175, Pseudomonas aeruginosa GPS 21, GSE 18, GSE 19, and GSE 30, and their cell-free culture filtrates were highly antagonistic to all the test fungi. The cell-free culture filtrates of these bacteria were fungicidal and induced mycelial deformations including hyphal bulging and vacuolization in necrotrophic fungi. The cell-free culture filtrates at 10% (v/v) concentration significantly inhibited the spore germination of biotrophic fungi. In the greenhouse, P. aeruginosa GSE 18 emerged as an effective biocontrol agent of collar rot closely followed by P. aeruginosa GSE 19. The bacterium applied as a seed treatment reduced the pre-emergence rotting and postemergence wilting by >60%. Pseudomonas aeruginosa GSE 18 effectively colonized the groundnut rhizosphere, both in native and in A. niger infested potting mixtures. Ninety-day-old peat formulation of P. aeruginosa GSE 18 had biocontrol ability comparable with the midlog-phase cells. Pseudomonas aeruginosa GSE 18, tolerant to thiram, in combination with the fungicide had an improved collar rot control. The present study was a successful attempt in selection of broad-spectrum and fungicide tolerant biocontrol agents that can be a useful component of integrated management of collar rot.Key words: Arachis, biocontrol, crown rot, peanut.

Broad-spectrum antifungal activity of spirooxindolo-pyrrolidine tethered indole/imidazole hybrid heterocycles against fungal pathogens

2019 ◽  
Vol 29 (16) ◽  
pp. 2059-2063 ◽  
Author(s):  
Mina Bolous ◽  
Natarajan Arumugam ◽  
Abdulrahman I. Almansour ◽  
Raju Suresh Kumar ◽  
Keiji Maruoka ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Broad Spectrum ◽  
Fungal Pathogens

scholarly journals Analysis of leaf microbiome composition of near-isogenic maize lines differing in broad-spectrum disease resistance

2019 ◽  
Author(s):  
Maggie R. Wagner ◽  
Posy E. Busby ◽  
Peter Balint-Kurti
Keyword(s):  
Disease Resistance ◽  
Broad Spectrum ◽  
Fungal Pathogens ◽  
List Type ◽  
Plant Genotype ◽  
Susceptible Parent ◽  
Host Genotype ◽  
Microbiome Composition ◽  
Resistant Lines ◽  
Disease Pressure

SummaryPlant genotype strongly affects disease resistance, and also influences the composition of the leaf microbiome. However, these processes have not been studied and linked in the microevolutionary context of breeding for improved disease resistance. We hypothesized that broad-spectrum disease resistance alleles also affect colonization by non-pathogenic symbionts.Quantitative trait loci (QTL) conferring resistance to multiple fungal pathogens were introgressed into a disease-susceptible maize inbred line. Bacterial and fungal leaf microbiomes of the resulting near-isogenic lines were compared to the microbiome of the disease-susceptible parent line at two timepoints in multiple fields.Introgression of QTL from disease-resistant lines strongly shifted the relative abundance of diverse fungal and bacterial taxa in both 3-week-old and 7-week-old plants. Nevertheless, the effects on overall community structure and diversity were minor and varied among fields and years. Contrary to our expectations, host genotype effects were not any stronger in fields with high disease pressure than in uninfected fields, and microbiome succession over time was similar in heavily infected plants and uninfected plants.These results show that introgressed QTL can greatly improve broad-spectrum disease resistance while having only limited and inconsistent pleiotropic effects on the leaf microbiome in maize.

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