{"doi":"10.1371/journal.pone.0327457","title":"ECDD-S16, a synthetic derivative of cleistanthin A, suppresses pyroptosis in Burkholderia pseudomallei-infected U937 macrophages","abstract":"<jats:sec id=\"sec024\">\n<jats:title>Background</jats:title>\n<jats:p>Melioidosis is an infectious disease caused by an intracellular Gram-negative bacterium, <jats:italic>Burkholderia pseudomallei,</jats:italic> which is a common cause of community-acquired sepsis in Southeast Asia and Northern Australia. The mortality rate in acute melioidosis patients, which is caused by sepsis, is very high (47.1%). Therefore, reducing inflammation may lead to the treatment of patients with acute melioidosis. Previously, ECDD-S16 was reported to be a potential compound for inhibiting inflammatory cell death (pyroptosis).</jats:p>\n</jats:sec>\n<jats:sec id=\"sec025\">\n<jats:title>Objective</jats:title>\n<jats:p>In this study, we further investigated the involvement of ECDD-S16 in pyroptosis induced by <jats:italic>B. pseudomallei</jats:italic> in the U937 human macrophage cell line.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec026\">\n<jats:title>Methods</jats:title>\n<jats:p>To investigate the biological activity of ECDD-S16, U937 macrophages were infected with <jats:italic>B. pseudomallei</jats:italic> before treatment with the compound. The expression of pyroptosis marker was determined by lactate dehydrogenase (LDH) assay, western blotting and ELISA assay. Additionally, the intracellular growth of <jats:italic>B. pseudomallei</jats:italic> was examined by CFU determination. Furthermore, colocalization of the bacteria with phagosome acidification was observed by immunofluorescent staining.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec027\">\n<jats:title>Results</jats:title>\n<jats:p>The results showed that ECDD-S16 decreased LDH release and levels of pyroptosis-related proteins in <jats:italic>B. pseudomallei</jats:italic>-infected cells by inhibiting phagolysosome acidification. Moreover, the attenuation of pyroptosis did not interfere with the intracellular survival of <jats:italic>B. pseudomallei</jats:italic> in U937 macrophages.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec028\">\n<jats:title>Conclusion</jats:title>\n<jats:p>Our findings indicated that ECDD-S16, a novel compound, interferes with caspase-1/4/5 activation, which may lead to the prevention of sepsis in acute melioidosis patients.</jats:p>\n</jats:sec>","journal":"PLOS One","year":2025,"id":647965,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1688399,"name":"Sucharat Sanongkiet","orcid":null,"position":1,"is_corresponding":false},{"id":1688401,"name":"Chularat Luangjindarat","orcid":null,"position":2,"is_corresponding":false},{"id":1688403,"name":"Sarut Thairat","orcid":null,"position":3,"is_corresponding":false},{"id":1688404,"name":"Bumrung Munyoo","orcid":null,"position":4,"is_corresponding":false},{"id":1688405,"name":"Napason Chabang","orcid":null,"position":5,"is_corresponding":false},{"id":1688407,"name":"Sitthivut Charoensutthivarakul","orcid":null,"position":6,"is_corresponding":false},{"id":1688409,"name":"Suparerk Borwornpinyo","orcid":null,"position":7,"is_corresponding":false},{"id":1688411,"name":"Patoomratana Tuchinda","orcid":null,"position":8,"is_corresponding":false},{"id":1450612,"name":"Marisa Ponpuak","orcid":"0000-0002-2889-1314","position":9,"is_corresponding":false},{"id":1688412,"name":"Pongsak Utaisincharoen","orcid":null,"position":10,"is_corresponding":false},{"id":1688414,"name":"Matsayapan Pudla","orcid":"0000-0001-8807-4124","position":11,"is_corresponding":false},{"id":1688397,"name":"Suphasuta Khongpraphan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"ECDD-S16, a synthetic derivative of cleistanthin A, suppresses pyroptosis in Burkholderia pseudomallei-infected U937 macrophages","abstract":"<jats:sec id=\"sec024\">\n<jats:title>Background</jats:title>\n<jats:p>Melioidosis is an infectious disease caused by an intracellular Gram-negative bacterium, <jats:italic>Burkholderia pseudomallei,</jats:italic> which is a common cause of community-acquired sepsis in Southeast Asia and Northern Australia. The mortality rate in acute melioidosis patients, which is caused by sepsis, is very high (47.1%). Therefore, reducing inflammation may lead to the treatment of patients with acute melioidosis. Previously, ECDD-S16 was reported to be a potential compound for inhibiting inflammatory cell death (pyroptosis).</jats:p>\n</jats:sec>\n<jats:sec id=\"sec025\">\n<jats:title>Objective</jats:title>\n<jats:p>In this study, we further investigated the involvement of ECDD-S16 in pyroptosis induced by <jats:italic>B. pseudomallei</jats:italic> in the U937 human macrophage cell line.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec026\">\n<jats:title>Methods</jats:title>\n<jats:p>To investigate the biological activity of ECDD-S16, U937 macrophages were infected with <jats:italic>B. pseudomallei</jats:italic> before treatment with the compound. The expression of pyroptosis marker was determined by lactate dehydrogenase (LDH) assay, western blotting and ELISA assay. Additionally, the intracellular growth of <jats:italic>B. pseudomallei</jats:italic> was examined by CFU determination. Furthermore, colocalization of the bacteria with phagosome acidification was observed by immunofluorescent staining.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec027\">\n<jats:title>Results</jats:title>\n<jats:p>The results showed that ECDD-S16 decreased LDH release and levels of pyroptosis-related proteins in <jats:italic>B. pseudomallei</jats:italic>-infected cells by inhibiting phagolysosome acidification. Moreover, the attenuation of pyroptosis did not interfere with the intracellular survival of <jats:italic>B. pseudomallei</jats:italic> in U937 macrophages.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec028\">\n<jats:title>Conclusion</jats:title>\n<jats:p>Our findings indicated that ECDD-S16, a novel compound, interferes with caspase-1/4/5 activation, which may lead to the prevention of sepsis in acute melioidosis patients.</jats:p>\n</jats:sec>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40627773","pmcid":"PMC12237264","openalex_id":"https://openalex.org/W4412108159","authors":[],"funders":[{"funder_name":"Mahidol University","grant_id":"","title":null}],"total_grants":1,"fwci":0.7403,"citation_percentile":0.71896428,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0327457&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0327457&type=printable","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.pone.0327457","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0327457","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40627773","host_type":"repository"},{"url":"https://doaj.org/article/c4472f428f0b459cad981188d8c8c556","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12237264","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12237264","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12237264?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Burkholderia infections and melioidosis","Inflammasome and immune disorders","Enzyme function and inhibition"],"mesh_terms":["Pyroptosis","Humans","Macrophages","Melioidosis","Burkholderia pseudomallei","U937 Cells"],"keywords":["Pyroptosis","Burkholderia pseudomallei","Melioidosis","Microbiology","Sepsis","U937 cell","Macrophage","Biology","Intracellular","Inflammation","Immunology","Bacteria","Inflammasome","Apoptosis","Biochemistry","In vitro"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T02:05:10.980539Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}