<p>Statins that target HMG-CoA reductase (HMGR) in the mevalonate pathway have been used to inhibit cholesterol biosynthesis. Therefore, they have the potential as inhibitors targeting the sterol biosynthesis pathway of plant pathogenic fungi. Currently, their activity against <i>Botrytis cinerea</i> is unknown. In this study, we determined the effects of four statins on both development and pathogenicity of <i>B. cinerea</i>. The interaction modes between statins and HMGR in <i>B. cinerea</i> were characterized through qRT-PCR and molecular docking analysis. Fluvastatin, atorvastatin, simvastatin and lovastatin strongly suppressed hyphal growth of <i>B. cinerea</i>, with EC<sub>50</sub> values of 0.66, 3.0, 10.0 and 22.21&#xa0;µg/mL respectively. Furthermore, statin treatment significantly decreased conidiation, inhibited conidia germination and germ tube elongation, reduced formation of infection structures and attenuated pathogenicity of <i>B. cinerea</i>. Expression levels of HMGR gene were upregulated under treatment with higher concentrations of statins. Molecular docking analysis further predicted that four statins bind to the active site of HMGR in <i>B. cinerea</i> through hydrophobic interactions, hydrogen bonds and salt-bridges. We demonstrated that statins exert inhibitory effects on mycelial growth, development and pathogenicity of <i>B. cinerea</i>, with HMGR predicted as the molecular target. These findings collectively indicated that HMGR was a potential novel control target and statins could be used as lead compounds for developing novel agents.</p>

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The effects and potential mechanisms of statins on growth, development and pathogenicity in Botrytis cinerea

  • Yang Peng,
  • Xiu Li,
  • Zhen Gao,
  • Ruilong Wang,
  • Xina Wu,
  • Yan Sun,
  • Xinhang Li,
  • Xinyu Yang

摘要

Statins that target HMG-CoA reductase (HMGR) in the mevalonate pathway have been used to inhibit cholesterol biosynthesis. Therefore, they have the potential as inhibitors targeting the sterol biosynthesis pathway of plant pathogenic fungi. Currently, their activity against Botrytis cinerea is unknown. In this study, we determined the effects of four statins on both development and pathogenicity of B. cinerea. The interaction modes between statins and HMGR in B. cinerea were characterized through qRT-PCR and molecular docking analysis. Fluvastatin, atorvastatin, simvastatin and lovastatin strongly suppressed hyphal growth of B. cinerea, with EC50 values of 0.66, 3.0, 10.0 and 22.21 µg/mL respectively. Furthermore, statin treatment significantly decreased conidiation, inhibited conidia germination and germ tube elongation, reduced formation of infection structures and attenuated pathogenicity of B. cinerea. Expression levels of HMGR gene were upregulated under treatment with higher concentrations of statins. Molecular docking analysis further predicted that four statins bind to the active site of HMGR in B. cinerea through hydrophobic interactions, hydrogen bonds and salt-bridges. We demonstrated that statins exert inhibitory effects on mycelial growth, development and pathogenicity of B. cinerea, with HMGR predicted as the molecular target. These findings collectively indicated that HMGR was a potential novel control target and statins could be used as lead compounds for developing novel agents.