BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Validation des hydrolases du peptidoglycane comme nouvelles cibles thérapeutiques contre l'infection à Helicobacter pylori

L infection à Helicobacter pylori touche près de 50 % de la population mondiale, et peut être associée à des pathologies sérieuses. De plus, l émergence de résistances bactériennes ne cesse d accroître le taux d échec thérapeutique, justifiant pleinement la recherche de nouvelles stratégies thérapeutiques. Dans ce sens, ce travail de thèse a eu pour objet de rechercher de nouvelles cibles thérapeutiques contre H. pylori, via la caractérisation d acteurs du métabolisme du peptidoglycane et de leur rôle dans la virulence bactérienne. Ainsi, nos travaux ont permis d une part, la caractérisation d une nouvelle peptidase bifonctionnelle du PG, HdpA, impliquée dans la virulence de H. pylori, via la régulation de sa forme bâtonnet, et d autre part, la mise en évidence de l action inhibitrice de la bulgécine sur la transglycosylase lytique Slt, engendrant une altération de la mobilité de H. pylori, ainsi qu une forte réduction de sa croissance par action synergique avec l amoxicilline.Helicobacter pylori is a major pathogen since it colonizes around 50 % of the world population and it can be associated to serious diseases. Moreover the emergence of bacterial resitances leads to more and more therapeutic failures, requiring the search for new therapeutic strategies. Consequently, the aim of that PhD work was to identify new therapeutic targets against H. pylori, via the characterization of peptidoglycan metabolism proteins, and their role in the bacterial virulence. Thereby, our work led firstly, to the characterization of a novel PG peptidase, involved in the virulence of H. pylori via its shape regulation, and secondly, to the study of the bulgecin, an inhibitor of the lytic transglycosylase Slt, provoking a bacterial motility defect and a strong growth decrease in presence of amoxicillin.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Identification of Genetic Markers for the Detection of <i>Bacillus thuringiensis</i> Strains of Interest for Food Safety

Bacillus thuringiensis (Bt), belonging to the Bacillus cereus (Bc) group, is commonly used as a biopesticide worldwide due to its ability to produce insecticidal crystals during sporulation. The use of Bt, especially subspecies aizawai and kurstaki, to control pests such as Lepidoptera, generally involves spraying mixtures containing spores and crystals on crops intended for human consumption. Recent studies have suggested that the consumption of commercial Bt strains may be responsible for foodborne outbreaks (FBOs). However, its genetic proximity to Bc strains has hindered the development of routine tests to discriminate Bt from other Bc, especially Bacillus cereus sensu stricto (Bc ss), well known for its involvement in FBOs. Here, to develop tools for the detection and the discrimination of Bt in food, we carried out a genome-wide association study (GWAS) on 286 complete genomes of Bc group strains to identify and validate in silico new molecular markers specific to different Bt subtypes. The analyses led to the determination and the in silico validation of 128 molecular markers specific to Bt, its subspecies aizawai, kurstaki and four previously described proximity clusters associated with these subspecies. We developed a command line tool based on a 14-marker workflow, to carry out a computational search for Bt-related markers from a putative Bc genome, thereby facilitating the detection of Bt of interest for food safety, especially in the context of FBOs

Identification of genetic markers for the discrimination of <i>Bacillus thuringiensis</i> within the <i>Bacillus cereus</i> group, in the context of foodborne outbreaks

AbstractBacillus thuringiensis (Bt), belonging to the Bacillus cereus (Bc) group, is commonly used as a biopesticide worldwide, due to its ability to produce insecticidal protein crystals during sporulation. The use of Bt, especially subspecies aizawai and kurstaki, to control pests such as Lepidoptera generally involves spraying mixtures containing spores and crystals on crops intended for human consumption. Recent studies have suggested that the consumption of commercial Bt strains may be responsible for foodborne outbreaks (FBOs). However, its genetic proximity to Bc strains has hindered the development of routine tests to discriminate Bt from other Bc, especially Bacillus cereus sensu stricto (Bc ss), also responsible for FBOs. Here, to develop tools for the detection and the discrimination of Bt in food, we carried out a genome-wide association study (GWAS) on 286 complete genomes of Bc group strains to identify and validate in silico new molecular markers specific to different Bt subtypes. The analyses led to the determination and the validation in silico of 128 molecular markers specific to Bt, its subspecies aizawai, kurstaki and four previously described proximity clusters associated with these subspecies. We developed a command line tool (https://github.com/afelten-Anses/Bt_typing) based on a 14-marker workflow for in silico Bt identification of a putative Bc genome with the aim of facilitating the discrimination of Bt from other Bc and between Bt subspecies, especially in the context of FBOs. Collectively, these data provide key elements for investigating Bc/Bt-associated FBOs and for monitoring Bt in food.</jats:p

Visualization of a substrate-induced productive conformation of the catalytic triad of the Neisseria meningitidis peptidoglycan O -acetylesterase reveals mechanistic conservation in SGNH esterase family members.

International audiencePeptidoglycan O-acetylesterase (Ape1), which is required for host survival in Neisseria sp., belongs to the diverse SGNH hydrolase superfamily, which includes important viral and bacterial virulence factors. Here, multi-domain crystal structures of Ape1 with an SGNH catalytic domain and a newly identified putative peptidoglycan-detection module are reported. Enzyme catalysis was performed in Ape1 crystals and key catalytic intermediates along the SGNH esterase hydrolysis reaction pathway were visualized, revealing a substrate-induced productive conformation of the catalytic triad, a mechanistic detail that has not previously been observed. This substrate-induced productive conformation of the catalytic triad shifts the established dogma on these enzymes, generating valuable insight into the structure-based design of drugs targeting the SGNH esterase superfamily

New Approach Methods to Assess the Enteropathogenic Potential of Strains of the Bacillus cereus Group, including Bacillus thuringiensis

Bacillus cereus (Bc) is a wide group of Gram-positive and spore-forming bacteria, known to be the etiological agents of various human infections, primarily food poisoning. The Bc group includes enteropathogenic strains able to germinate in the digestive tract and to produce enterotoxins such as Nhe, Hbl, and CytK. One species of the group, Bacillus thuringiensis (Bt), has the unique feature of producing insecticidal crystals during sporulation, making it an important alternative to chemical pesticides to protect crops from insect pest larvae. Nevertheless, several studies have suggested a link between the ingestion of pesticide strains and human cases of food poisoning, calling their safety into question. Consequently, reliable tools for virulence assessment are worth developing to aid decision making in pesticide regulation. Here, we propose complementary approaches based on two biological models, the human intestinal Caco-2 cell line and the insect Drosophila melanogaster, to assess and rank the enteric virulence potency of Bt strains in comparison with other Bc group members. Using a dataset of 48 Bacillus spp. strains, we showed that some Bc group strains, including Bt, were able to induce cytotoxicity in Caco-2 cells with concomitant release of IL-8 cytokine, a landmark of pro-inflammatory response. In the D. melanogaster model, we were able to sort a panel of 39 strains into four different classes of virulence, ranging from no virulence to strong virulence. Importantly, for the most virulent strains, mortality was associated with a loss of intestinal barrier integrity. Interestingly, although strains can share a common toxinotype, they display different degrees of virulence, suggesting the existence of specific mechanisms of virulence expression in vivo in the intestine