The Pomacea canaliculata,also known as apple snail,is an invasive species in China,posing a serious threat to agricultural production and public health.To prevent its rampant infestation,we developed a highly efficien...The Pomacea canaliculata,also known as apple snail,is an invasive species in China,posing a serious threat to agricultural production and public health.To prevent its rampant infestation,we developed a highly efficient snail-killing lead compound,1-(4-chlorophenyl)-3-(pyridin-3-yl)urea(PBQ).However,the killing mechanism of PBQ remains unclear.To elucidate this,two novel compounds,B-PBQ and J-PBQ,were developed through structural modification of PBQ and were used,through both protein pull-down assay and confocal laser scanning microscopy imaging,to identify and confirm that phosphofructokinase(PFK)in the apple snail is the primary target protein of PBQ.Further studies revealed that PBQ successfully inhibits the activity,content,and expression of PFK in apple snail,disrupting the glycolysis pathway and leading to abnormal energy production.These disruptions impair the snail's tolerance to low oxygen,resulting in its efficient eradication.These findings offer a promising direction for developing next-generation PFK-targeted snail-killing pesticides.Furthermore,the strategy of combining pull-down assays with optical imaging used in this work provides a novel approach for the exploration of mechanisms of other pesticide candidates.展开更多
基金supported by the National Natural Science Foundation of China(82072309,22067019,22367023,32160236)the Major Science and Technology Project of Yunnan Province(202402AE090006)+1 种基金the Yunnan Provincial Science and Technology Department-Yunnan University Joint Special Project(202201BF070001-001)the Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai(2023–2025)Key Discipline Project(GWV111.1-12)。
文摘The Pomacea canaliculata,also known as apple snail,is an invasive species in China,posing a serious threat to agricultural production and public health.To prevent its rampant infestation,we developed a highly efficient snail-killing lead compound,1-(4-chlorophenyl)-3-(pyridin-3-yl)urea(PBQ).However,the killing mechanism of PBQ remains unclear.To elucidate this,two novel compounds,B-PBQ and J-PBQ,were developed through structural modification of PBQ and were used,through both protein pull-down assay and confocal laser scanning microscopy imaging,to identify and confirm that phosphofructokinase(PFK)in the apple snail is the primary target protein of PBQ.Further studies revealed that PBQ successfully inhibits the activity,content,and expression of PFK in apple snail,disrupting the glycolysis pathway and leading to abnormal energy production.These disruptions impair the snail's tolerance to low oxygen,resulting in its efficient eradication.These findings offer a promising direction for developing next-generation PFK-targeted snail-killing pesticides.Furthermore,the strategy of combining pull-down assays with optical imaging used in this work provides a novel approach for the exploration of mechanisms of other pesticide candidates.
