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This process facilitates the spread of clinical traits such as antibiotic resistance. The DNA uptake specificity is mediated by conserved motifs found in certain naturally transformable species. Despite its evolutionary and clinical significance, dedicated resources for natural transformation have been lacking. Here, we present the Natural Transformation DataBase (NTDB) (https:\/\/bioinfo-mml.sjtu.edu.cn\/NTDB\/), which compiles information on machinery and regulatory genes associated with natural transformation in prokaryotes. NTDB integrated experimentally validated data on 118 naturally transformable species, 1072 transformation-associated genes, and 10 DNA uptake motifs identified through literature mining. Homology-based search identified 420\u2009600 machinery genes and 246\u2009164 regulatory genes across 12\u2009310 prokaryotic strains, with comprehensive protein annotations. In addition, the distribution and abundance of DNA uptake motifs in Neisseriaceae and Pasteurellaceae species were quantified. Furthermore, NTDB offers online tools to predict natural transformation-associated genes and DNA uptake motifs via an interactive web interface. NTDB intends to facilitate mechanistic studies of natural transformation machinery and competence regulation.<\/jats:p>","DOI":"10.1093\/nar\/gkag1000","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T08:33:03Z","timestamp":1792398783000},"source":"Crossref","is-referenced-by-count":0,"title":["NTDB: a curated database of natural transformation machinery and regulatory genes in prokaryotes"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2909-7064","authenticated-orcid":false,"given":"Jiahao","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai 200233 ,","place":["China"]},{"name":"State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University , Shanghai 200240 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runze","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University , Shanghai 200240 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency & Research and Translational Laboratory of Acute Injury and Secondary Infection, Minhang Hospital, Fudan University , Shanghai 201199 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4117-793X","authenticated-orcid":false,"given":"Marco R","family":"Oggioni","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, University of Bologna , Bologna 40126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Tai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University , Shanghai 200240 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai 200233 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9439-1660","authenticated-orcid":false,"given":"Hong-Yu","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai 200233 ,","place":["China"]},{"name":"State Key Laboratory of Microbial Metabolism, Joint International Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University , Shanghai 200240 ,","place":["China"]},{"name":"Shanghai Key Laboratory of Severe Respiratory Infection , Shanghai 200025 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