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El Houdaigui, B.

Publications and source records attributed to El Houdaigui, B..

2 recordsLinked to original sources

A comprehensive AMR genotype-phenotype database (CABBAGE)

Addressing the growing threat of antimicrobial resistance (AMR) requires the development of large-scale resources that link bacterial genomic data with phenotypic antimicrobial resistance profiles. Such datasets are essential for advancing genotype-based predictions of resistance to uncover novel resistance mechanisms, as well as identifying and tracking global trends. Here, we describe the development of the Comprehensive Assessment of Bacterial-Based AMR prediction from GEnotypes (CABBAGE) database, linking bacterial genomes to associated antibiotic susceptibility data and relevant metadata across WHO Bacterial Priority Pathogens, sourced from both publications and existing databases, and curated into a format that is compatible with, and extends, both NCBI and ENA formats. The resulting CABBAGE database, comprising over 170,000 unique sequenced isolates and approximately 1.7 million genome-phenotype pairs linked to extensive metadata, represents the largest database of its kind, consolidating existing AMR phenotype-genotype data into a single unified format. CABBAGE encompasses a broad range of antimicrobials, facilitating the analysis of global resistance trends as well as benchmarks of genotype-to-phenotype predictive methods, and empowering further research uses. The database is freely accessible at https://www.ebi.ac.uk/amr and is currently being integrated with the BioSample database, enabling easy access for the AMR research community.

genomics↗

Bacterial genome architecture shapes global transcriptional regulation by DNA supercoiling

DNA supercoiling acts as a global transcriptional regulator in bacteria, that plays an important role in adapting their expression programme to environmental changes, but for which no quantitative or even qualitative regulatory model is available. Here, we focus on spatial supercoiling heterogeneities caused by the transcription process itself, which strongly contribute to this regulation mode. We propose a new mechanistic modeling of the transcription-supercoiling dynamical coupling along a genome, which allows simulating and quantitatively reproducing in vitro and in vivo transcription assays, and highlights the role of genes local orientation in their supercoiling sensitivity. Consistently with predictions, we show that chromosomal relaxation artificially induced by gyrase inhibitors selectively activates convergent genes in several enterobacteria, while conversely, an increase in DNA supercoiling naturally selected in a long-term evolution experiment with Escherichia coli favours divergent genes. Simulations show that these global expression responses to changes in DNA supercoiling result from fundamental mechanical constraints imposed by transcription, independently from more specific regulation of each promoter. These constraints underpin a significant and predictable contribution to the complex rules by which bacteria use DNA supercoiling as a global but fine-tuned transcriptional regulator.

microbiology↗