Sensitivity of Pythium spp. and Phytopythium spp. and tolerance mechanism of Pythium spp. to oxathiapiprolin

Miao, Jianqiang; Liu, Xiaofei; Du, Xiaoran; Li, Guixiang; Li, Chengcheng; Zhao, Deyou; Liu, Xili

doi:10.1002/ps.5946

Cited by 14 publications

(6 citation statements)

References 31 publications

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“…It is worth noting that the other three fungicides (i.e., mandipropamid, oxathiapiproline, and dimethomorph) are effective against the oomycetes, primarily Phytophthora and Pseudoperonospora species ( 15 , 27 ). However, we found these chemicals failed to markedly inhibit P. insidiosum , which is not a surprise since they also reportedly fail to control other Pythium species ( 61 , 62 ), underlying the biological diversity among closely related oomycetes.…”

Section: Discussionmentioning

confidence: 59%

Potential anti- Pythium insidiosum therapeutics identified through screening of agricultural fungicides

Yolanda,

Jearawuttanakul,

Wannalo

et al. 2024

Microbiol Spectr

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Pythiosis is a life-threatening infectious disease caused by the oomycete Pythium insidiosum . Clinical manifestations of pythiosis include an eye, blood vessel, skin, or gastrointestinal tract infection. Pythiosis has been increasingly reported worldwide, with an overall mortality rate of 28%. Radical surgery is required to save patients’ lives due to the limited efficacy of antimicrobial drugs. Effective medical treatments are urgently needed for pythiosis. This study aims to find anti- P . insidiosum agents by screening 17 agricultural fungicides that inhibit plant-pathogenic oomycetes and validating their efficacy and safety. Cyazofamid outperformed other fungicides as it can potently inhibit genetically diverse P. insidiosum isolates while exhibiting minimal cellular toxicities. The calculated therapeutic scores determined that the concentration of cyazofamid causing significant cellular toxicities was eight times greater than the concentration of the drug effectively inhibiting P. insidiosum . Furthermore, other studies showed that cyazofamid exhibits low-to-moderate toxicities in animals. The mechanism of cyazofamid action is likely the inhibition of cytochrome b , an essential component in ATP synthesis. Molecular docking and dynamic analyses depicted a stable binding of cyazofamid to the Qi site of the P. insidiosum ’s cytochrome b orthologous protein. In conclusion, our search for an effective anti- P . insidiosum drug indicated that cyazofamid is a promising candidate for treating pythiosis. With its high efficacy and low toxicity, cyazofamid is a potential chemical for treating pythiosis, reducing the need for radical surgeries, and improving recovery rates. Our findings could pave the way for the development of new and effective treatments for pythiosis. IMPORTANCE Pythiosis is a severe infection caused by Pythium insidiosum . The disease is prevalent in tropical/subtropical regions. This infectious condition is challenging to treat with antifungal drugs and often requires surgical removal of the infected tissue. Pythiosis can be fatal if not treated promptly. There is a need for a new treatment that effectively inhibits P. insidiosum . This study screened 17 agricultural fungicides that target plant-pathogenic oomycetes and found that cyazofamid was the most potent in inhibiting P. insidiosum . Cyazofamid showed low toxicity to mammalian cells and high affinity to the P. insidiosum’s cytochrome b , which is involved in energy production. Cyazofamid could be a promising candidate for the treatment of pythiosis, as it could reduce the need for surgery and improve the survival rate of patients. This study provides valuable insights into the biology and drug susceptibility of P. insidiosum and opens new avenues for developing effective therapies for pythiosis.

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Section: Discussionmentioning

confidence: 59%

Potential anti- Pythium insidiosum therapeutics identified through screening of agricultural fungicides

Yolanda,

Jearawuttanakul,

Wannalo

et al. 2024

Microbiol Spectr

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“…Notably, only a few drugs and one cyclic antifungal peptide from marine fungi have shown inhibitory effects against soybean phytophthora blight [ 21 , 22 , 23 , 24 ]. Interestingly, Fluoxapiprolin, Oxzthiapiprolin, and Ethaboxam, developed by Bayer and DuPont (Wilmington, DE, USA), have demonstrated the ability to inhibit the growth of P. sojae by targeting spores and mycelium ( Figure 1 ) [ 25 , 26 , 27 , 28 ]. However, it is worth noting that these compounds belong to the thiazole class, and mutations in the single dominant genes (Rps) and β-tubulin have been identified as potential causes of drug resistance [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Ran,

Shehzadi,

Liang

et al. 2024

IJMS

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Soybean phytophthora blight is a severe menace to global agriculture, causing annual losses surpassing USD 1 billion. Present crop loss mitigation strategies primarily rely on chemical pesticides and disease-resistant breeding, frequently surpassed by the pathogens’ quick adaptive evolution. In this urgent scenario, our research delves into innovative antimicrobial peptides characterized by low drug resistance and environmental friendliness. Inhibiting chitin synthase gene activity in Phytophthora sojae impairs vital functions such as growth and sporulation, presenting an effective method to reduce its pathogenic impact. In our study, we screened 16 previously tested peptides to evaluate their antimicrobial effects against Phytophthora using structure-guided drug design, which involves molecular docking, saturation mutagenesis, molecular dynamics, and toxicity prediction. The in silico analysis identified AMP_04 with potential inhibitory activity against Phytophthora sojae’s chitin synthase. Through three rounds of saturation mutagenesis, we pin-pointed the most effective triple mutant, TP (D10K, G11I, S14L). Molecular dynamic simulations revealed TP’s stability in the chitin synthase-TP complex and its transmembrane mechanism, employing an all-atom force field. Our findings demonstrate the efficacy of TP in occupying the substrate-binding pocket and translocation catalytic channel. Effective inhibition of the chitin synthase enzyme can be achieved. Specifically, the triple mutant demonstrates enhanced antimicrobial potency and decreased toxicity relative to the wild-type AMP_04, utilizing a mechanism akin to the barrel-stave model during membrane translocation. Collectively, our study provides a new strategy that could be used as a potent antimicrobial agent in combatting soybean blight, contributing to sustainable agricultural practices.

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“…16 Oxathiapiprolin exhibits extremely high activity against plant oomycete pathogens. [15][16][17][18][19] Recently, oxathiapiprolin was registered for the control of Phytophthora infestans, Phytophthora capsici, Pseudoperonospora cubensis, and Plasmopara viticola in China. However, no data are available on the baseline sensitivity or action mechanism of oxathiapiprolin against Phytophthora sojae, or on its efficacy for controlling soybean PRR.…”

Section: Introductionmentioning

confidence: 99%

“…Oxathiapiprolin [Fungicide Resistance Action Committee (FRAC) code 49] is a new piperidinyl thiazole isoxazoline fungicide developed by Dupont Crop Protection 15 and commercialized by Corteva Agriscience 16 . Oxathiapiprolin exhibits extremely high activity against plant oomycete pathogens 15–19 . Recently, oxathiapiprolin was registered for the control of Phytophthora infestans , Phytophthora capsici , Pseudoperonospora cubensis , and Plasmopara viticola in China.…”

Section: Introductionmentioning

confidence: 99%

Use of oxathiapiprolin for controlling soybean root rot caused by Phytophthora sojae: efficacy and mechanism of action

Wang

et al. 2022

Pest Management Science

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Background: Oxathiapiprolin is a new isoxazoline fungicide developed by DuPont to control oomycete diseases. Although oxathiapiprolin has shown strong inhibitory activity against oomycete pathogens, little is known about its ability to control Phytophthora sojae.Results: Oxathiapiprolin showed high inhibitory activity against Phytophthora sojae, with 50% effective concentration (EC 50 ) values ranging from 1.15 × 10 −4 to 4.43 × 10 −3 ∼g mL −1 . Oxathiapiprolin inhibited various stages of Phytophthora sojae development, including mycelial growth, sporangium formation, oospore production, and zoospore release. Electron microscopy studies revealed that oxathiapiprolin caused severe morphological and ultrastructural damage to Phytophthora sojae. Oxathiapiprolin affected the cell membrane and wall of Phytophthora sojae, making it more sensitive to osmotic and cell wall stress. Oxathiapiprolin exhibited translocation activity; it was absorbed by soybean roots and then translocated to the leaves. It was effective at reducing soybean Phytophthora root rot under glasshouse and field conditions. Both fungicide seed treatment and foliar spray significantly reduced disease incidence and yield losses compared with untreated controls in the field. Conclusion:Oxathiapiprolin exhibits high inhibitory activity against Phytophthora sojae, and has multiple mechanisms of action including severe mycelial damage and modulation of osmotic and cell wall stress. These results indicate that oxathiapiprolin can be used at low concentrations for highly effective management of soybean Phytophthora root rot caused by Phytophthora sojae.

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Sensitivity of Pythium spp. and Phytopythium spp. and tolerance mechanism of Pythium spp. to oxathiapiprolin

Cited by 14 publications

References 31 publications

Potential anti- Pythium insidiosum therapeutics identified through screening of agricultural fungicides

Potential anti- Pythium insidiosum therapeutics identified through screening of agricultural fungicides

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Use of oxathiapiprolin for controlling soybean root rot caused by Phytophthora sojae: efficacy and mechanism of action

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