Biology subjects

Ba, M.

Publications and source records attributed to Ba, M..

4 recordsLinked to original sources

bioRxiv2025

Atypical thioredoxin Patrx2 enhances alginate production in mucoid Pseudomonas aeruginosa

Pseudomonas aeruginosa, an opportunistic human pathogen, is known for its ability to respond and adapt to its environment, employing intricate adaptation mechanisms that can lead to the formation of complex biofilms. Redox processes play a pivotal role in bacterial adaptation mechanisms. The cytoplasm of most organisms is recognized for maintaining a reducing environment through thiol-disulfide oxidoreductases. In Pseudomonas aeruginosa, we have identified an unusual cytoplasmic thioredoxin named Patrx2. What sets Patrx2 apart is its active site, which contains a consensus sequence, CGHC, identical to the characteristic motif of protein disulfide isomerases (PDIs) found in eukaryotic cells. Our investigations have unveiled that Patrx2, unlike canonical thioredoxins, exhibits disulfide isomerase activity in vitro and displays physicochemical properties, as well as a structural conformation of its catalytic site, reminiscent of PDIs. Using a mutant transposon library, we found that the expression of patrx2 is regulated by the alternative sigma factor AlgU, which plays a crucial role in the formation of alginate biofilms in P. aeruginosa. We further demonstrated strong patrx2 expression in a mucoid strain we constructed, carrying the clinically relevant mucA22 mutation frequently found in cystic fibrosis patients. Furthermore, our results showed a significant decrease in alginate synthesis in a patrx2 mutant in this mucoid strain, which we attributed to its catalytic activity in a C34S variant. The study of Patrx2, an atypical thioredoxin expressed within an alginate biofilm, underscores the importance of redox regulation in adaptation mechanisms. Patrx2s involvement in alginate biosynthesis opens new pathway for inhibiting biofilm synthesis. HighlightsO_LIThe patrx2 gene is regulated by the alternative sigma factor AlgU C_LIO_LIPatrx2 is strongly produced in mucoid P. aeruginosa C_LIO_LIPatrx2 is an atypical thioredoxin with disulfide isomerase activity C_LIO_LIPatrx2 impacts alginate production in the mucoid P. aeruginosa mucA22 strain, likely through redox regulation of alginate biosynthesis. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/667166v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@14f304forg.highwire.dtl.DTLVardef@1ecc15eorg.highwire.dtl.DTLVardef@8b18d9org.highwire.dtl.DTLVardef@c71b7_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

MilkOligoCorpus: a semantically annotated resource for knowledge extraction on mammalian milk oligosaccharides

Milk oligosaccharides are bioactive components that regulate the composition of the neonatal microbiota and exert immunomodulatory functions. Their beneficial effects depend on their structure. Numerous studies have shown intra- and inter-species variation in the structural composition and concentration of these compounds in mammalian milk, yet the biological significance of such variation remains poorly understood. Automated natural language processing methods are promising tools for extracting and gathering structured data from unstructured texts to get insight into the biological significance of milk oligosaccharide variation across mammals. These methods require training and evaluation on manually annotated text corpora. While annotated corpora exist for chemical substances, none are specifically designed for training natural language processing models to extract information on milk oligosaccharides. To this end, we propose MilkOligoCorpus, a new gold standard for milk oligosaccharide composition in mammalian species. MilkOligoCorpus annotation scheme is a rich entity/relation model designed to describe the diversity pattern of milk oligosaccharides according to female factor variability and to help better understand the structure-related function of milk oligosaccharides. MilkOligoCorpus consists of 30 PubMed texts fully annotated with entities related to individuals, samples, oligosaccharides and oligosaccharide quantification linked by binary and n-ary relationships. To address data interoperability across disparate publications and databases, four terminological resources were also developed to assign unique identifiers to the entities, supported by external ontologies. This paper presents the creation of the MilkOligoCorpus and its associated schema, along with the development of annotation guidelines and terminological resources. We also present experimental results obtained by baseline information extraction models on the corpus.

bioinformatics↗

bioRxiv2022

Omnicrobe, an open-access database of microbial habitats and phenotypes using a comprehensive text mining and data fusion approach

The dramatic increase in the amount of microbe descriptions in databases, reports and papers presents a two-fold challenge for accessing the information: integration of heterogeneous data in a standard ontology-based representation and normalization of the textual descriptions by semantic analysis. Recent text mining methods offer powerful ways to extract textual information and generate ontology-based representation. This paper describes the design of the Omnicrobe application that gathers comprehensive information on habitats, phenotypes and usages of microbes from scientific sources of high interest to the microbiology community. The Omnicrobe database contains around 1 million descriptions of microbe properties that are created by analyzing and combining six information sources of various kinds, i.e. biological resource catalogues, sequence database and scientific literature. The microbe properties are indexed by the Ontobiotope ontology and their taxa are indexed by an extended version of the taxonomy maintained by the National Center for Biotechnology Information. The Omnicrobe application covers all domains of microbiology. It provides an easy-to-use support in the resolution of scientific questions related to the habitats, phenotypes and uses of microbes through simple and complex ontology-based queries. We illustrate the potential of Omnicrobe with a use case from the food innovation domain.

bioinformatics↗

bioRxiv2021

Discovery of SARS-CoV-2 papain-like protease inhibitors through a combination of high-throughput screening and FlipGFP-based reporter assay

The papain-like protease (PLpro) of SARS-CoV-2 is a validated antiviral drug target. PLpro is involved in the cleavage of viral polyproteins and antagonizing host innate immune response through its deubiquitinating and deISG15ylating activities, rendering it a high profile antiviral drug target. Through a FRET-based high-throughput screening, several hits were identified as PLpro inhibitors with IC50 values at the single-digit micromolar range. Subsequent lead optimization led to potent inhibitors with IC50 values ranging from 0.56 to 0.90 {micro}M. To help prioritize lead compounds for the cellular antiviral assay against SARS-CoV-2, we developed the cell-based FlipGFP assay that is suitable for quantifying the intracellular enzymatic inhibition potency of PLpro inhibitors in the BSL-2 setting. Two compounds selected from the FlipGFP-PLpro assay, Jun9-53-2 and Jun9-72-2, inhibited SARS-CoV-2 replication in Caco-2 hACE2 cells with EC50 values of 8.89 and 8.32 {micro}M, respectively, which were 3-fold more potent than GRL0617 (EC50 = 25.1 {micro}M). The X-ray crystal structures of PLpro in complex with GRL0617 showed that binding of GRL0617 to SARS-CoV-2 induced a conformational change in the BL2 loop to the more closed conformation. Overall, the PLpro inhibitors identified in this study represent promising starting points for further development as SARS-CoV-2 antivirals, and FlipGFP-PLpro assay might be a suitable surrogate for screening PLpro inhibitors in the BSL-2 setting.

pharmacology and toxicology↗