Natural transformation, genetically controlled by specialized machinery and regulatory genes, drives evolution and adaptation in prokaryotes. 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 420 600 machinery genes and 246 164 regulatory genes across 12 310 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.
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Guan et al. (2026) studied this question.
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