Biology subjects

Poirel, L.

Publications and source records attributed to Poirel, L..

5 recordsLinked to original sources

bioRxiv2026

An Integrated Miniaturized Metabologenomics Workflow for High-Throughput Actinomycetes Prioritization

Antibiotic resistance is a growing global health threat, while the discovery of new antimicrobial agents remains constrained by labor-intensive cultivation, extraction, and screening workflows. We developed a miniaturized, high-throughput metabologenomics workflow integrating Duetz system-based microfermentation, extraction-free UHPLC-HRMS/MS profiling, antibacterial screening, and genome mining. A collection of 80 soil-derived actinomycetes was screened against clinically relevant pathogens, identifying seven isolates active against methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecium, or both. All isolates were cultivated in Duetz system-based microfermentation plates, and cell-free culture filtrates were analyzed directly by UHPLC-HRMS/MS without solvent extraction. Compared with a conventional workflow, the approach reduced culture-medium consumption by approximately 99%, decreased recurring consumable costs by approximately 96%, and reduced the time required to obtain LC-MS-ready samples from typically 5 days to approximately 20 min. Integration of antibacterial, metabolomic, and genomic datasets supported the annotation of diverse metabolite families, including actinomycins, polyether ionophores, ansamycins, angucyclines, hydroxamate siderophores, ectoines, tambromycin-associated metabolites, and putative lydicamycin metabolites. Selected annotations were validated using commercial standards. Overall, this study demonstrates that integrating miniaturized Duetz system-based cultivation, extraction-free metabolomics, antibacterial screening, and genome mining provides a scalable, robust, and cost-effective platform for high-throughput strain prioritization and natural product discovery.

microbiology↗

bioRxiv2025

Influence of iron uptake systems on cefiderocol activity in Escherichia coli: at the crossroads of antibiotic resistance and virulence

Cefiderocol (FDC) is a new siderophore-conjugated cephalosporin that enters the periplasm via iron transport systems. However, the specific contribution of individual iron uptake pathways to FDC activity remains unclear. We investigated the role of 12 iron acquisition systems using several Escherichia coli strain collections. FDC MICs were determined in iron-depleted and iron-supplemented media for E. coli mutants (Keio and pathogenic island [PAI]-deleted collections) and for clinical wild-type or TEM-producing E. coli (WT/TEM-Ec) and NDM-producing (NDM-Ec) isolates. The distribution of iron uptake genes was assessed in these isolates. In addition, fec operon prevalence and genomic location were investigated in E. coli genomes from EnteroBase and RefSeq databases. Among Keio and 536-PAI-deleted mutants, only {Delta}cirA and {Delta}fiu (enterobactin system) showed increased FDC MICs (8- and 3-fold, respectively), while {Delta}fecA and {Delta}fecB had lower MICs (3-fold decrease). The fec operon, a known extraintestinal virulence factor, was significantly more prevalent in isolates with FDC MICs above median than in those with MICs below (94% vs. 38% in WT/TEM-Ec; 100% vs. 0% in NDM-Ec). According to EUCAST breakpoints, 66.7% of fec-positive NDM-Ec were resistant to FDC while none of the fec-negative were. The fec operon was found in 46.5% of E. coli genomes, including virulent clones (ST131, 77%) and was mostly chromosome-borne (99%). Plasmid-borne fec closely resembled that of Enterobacter hormaechei, suggesting interspecies transfer. Our findings highlight the role of Fec in reducing FDC susceptibility and promoting resistance in NDM-producing E. coli. They challenge the virulence-resistance trade-off demonstrating the liaisons dangereuses between iron and antibiotics.

microbiology↗

bioRxiv2023

Inter-phylum circulation of a beta-lactamase - encoding gene: a rare but observable event

Beta-lactam degradation by beta-lactamases is the most common mechanism of beta-lactam resistance in Gram-negative bacteria. Beta-lactamase encoding genes can be transferred between closely-related bacteria, but spontaneous inter-phylum transfers (between distantly related bacteria) has never been reported. Here, we describe an extended-spectrum beta-lactamase (ESBL)-encoding gene (blaMUN-1) shared between the Peudomonadota and Bacteroidota phyla. An Escherichia coli strain was isolated from a patient in Munster (Germany). Its genome was sequenced (Illumina and Nanopore). The ESBL encoding gene was cloned and the corresponding enzyme was characterised. Distribution of the gene among bacteria was studied with BLASTN using RefSeq Genomes databases. Frequency of its closest homolog in the Global Microbial Gene Catalog (GMGC) was also analysed. The blaMUN-1 gene found in the E. coli strain, encoded for an Ambler subclass A2 beta-lactamase with 82.2% amino acid identity to TLA-1 and it was found to confer an ESBL phenotype. blaMUN-1 was found in four copies, two chromosomal copies and two located on a phage-plasmid p0111. Each copy was found on a 7.6kb genomic island associated with mobility. blaMUN-1 was found distributed among the Bacteroidales order and in Sutterella wardsworthensis (Pseudomonadota). Its closest homolog in the GMGC was found predominantly and frequently in the Human gut sub-catalog (found in 26.8% of the samples). This is the first reported case of inter-phylum transfer of an ESBL-encoding gene, between the Bacteroidota and Pseudomonadota phyla. While the gene was frequently found in the human gut, inter-phylum transfer was rare, suggesting that inter-phylum barriers are strong but not impassable.

microbiology↗

bioRxiv2023

Emergence of Acinetobacter baumannii International Clone 10 predominantly found in the Middle East

Acinetobacter baumannii is a globally distributed human pathogen. Infections caused by carbapenem-resistant isolates of A. baumannii (CRAB) are of great concern, as treatment options are very limited. Despite having among the highest rates reported worldwide, there exists limited genomic data from CRAB strains isolated in the Middle East. Here we report epidemiological, phenotypic, and genome sequencing data (short reads and long reads) on a set of 60 A. baumannii isolates belonging to Sequence Type ST158 (Pasteur MLST scheme). They represent a novel international clone (IC), designated IC10, with limited geographic spread beyond the Middle East. Specific antibiotic-resistance genes associated with this clone were identified and data on the plasmid content associated with this lineage are presented.

microbiology↗

bioRxiv2021

Chlorhexidine reduced susceptibility associated to tetracycline resistance in clinical isolates of Escherichia coli

Chlorhexidine is a widely used antiseptic in hospital and community healthcare. Decreased susceptibility to this compound has been recently described in Klebsiella pneumoniae and Pseudomonas aeruginosa, together with cross-resistance to colistin. Surprisingly, few data are available for Escherichia coli, the main species responsible for community and healthcare-associated infections. In order to decipher chlorhexidine resistance mechanisms in E. coli, we studied both in vitro derived and clinical isolates through whole-genome sequence analysis. Comparison of strains grown in vitro under chlorhexidine pressure identified mutations in the gene mlaA coding for a phospholipid transport system. Phenotypic analyses of single-gene mutant from the Keio collection confirmed the role of this mutation in the decreased susceptibility to chlorhexidine. However, mutations in mlaA were not found in isolates from large clinical collections. In contrast, genome wide association studies (GWAS) showed that, in clinical strains, chlorhexidine reduced susceptibility was associated with the presence of tetA genes of class B coding for efflux pumps and located in a Tn10 transposon. Construction of recombinant strains in E. coli K-12 confirmed the role of tetA determinant in acquired resistance to both chlorhexidine and tetracycline. Our results reveal two different evolutionary paths leading to chlorhexidine decreased susceptibility: one restricted to in vitro evolution conditions and involving a retrograde phospholipid transport system; the other observed in clinical isolates associated with efflux pump TetA. None of these mechanisms provides cross-resistance to colistin or to the cationic surfactant octenidine. This work demonstrates the GWAS power to identify new resistance mechanisms in bacterial species.

microbiology↗