{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang H"],"funding":["National Natural Science Foundation of China","National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["16"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12769697"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(1)"],"pubmed_abstract":["Host-directed antibacterial compounds remain underdeveloped for intracellular pathogens. Here, we identify Dehydroevodiamine (DEHD) as a broad-spectrum host-directed antibiotics that inhibits intracellular bacterial replication (Salmonella, E. coli, S. aureus, etc.) and synergizes with antibiotics in vitro and in vivo. Structural analyses reveal DEHD directly binds MDM2 (KD=68.34 μM), activating the MDM2-P53-V-ATPases axis to maintain lysosomal acidity through V-ATPase activity and induce mTOR-dependent autophagy. This mechanism enhances antibiotic efficacy against resistant pathogens, reducing mortality from 90% to 10% in lethal murine infections. Our work establishes lysosomal activation via the MDM2-P53-V-ATPases axis as a potent host-directed strategy, with DEHD providing a promising l"],"journal":["Communications biology"],"pubmed_title":["MDM2-P53-V-ATPases axis driven by dehydroevodiamine to fight intracellular bacterial infection."],"pmcid":["PMC12769697"],"funding_grant_id":["U22A20523"],"pubmed_authors":["Xu L","Wang N","Kong L","He X","Ma H","Wang H","Wang Y","Wang J","Niu X","Deng X","Wang L"],"additional_accession":[]},"is_claimable":false,"name":"MDM2-P53-V-ATPases axis driven by dehydroevodiamine to fight intracellular bacterial infection.","description":"Host-directed antibacterial compounds remain underdeveloped for intracellular pathogens. Here, we identify Dehydroevodiamine (DEHD) as a broad-spectrum host-directed antibiotics that inhibits intracellular bacterial replication (Salmonella, E. coli, S. aureus, etc.) and synergizes with antibiotics in vitro and in vivo. Structural analyses reveal DEHD directly binds MDM2 (KD=68.34 μM), activating the MDM2-P53-V-ATPases axis to maintain lysosomal acidity through V-ATPase activity and induce mTOR-dependent autophagy. This mechanism enhances antibiotic efficacy against resistant pathogens, reducing mortality from 90% to 10% in lethal murine infections. Our work establishes lysosomal activation via the MDM2-P53-V-ATPases axis as a potent host-directed strategy, with DEHD providing a promising l","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-06T11:08:01.434Z","creation":"2026-05-29T03:12:39.434Z"},"accession":"S-EPMC12769697","cross_references":{"pubmed":["41390711"],"doi":["10.1038/s42003-025-09251-w"]}}