Biology subjects

Bridier-Nahmias, A.

Publications and source records attributed to Bridier-Nahmias, A..

5 recordsLinked to original sources

bioRxiv2024

CONSTRUCT: an algorithmic tool for identifying functional or structurally important regions in protein tertiary structure

In the realm of protein-coding genes, evolutionary rates show considerable variability. Essential or highly expressed proteins evolve more slowly, and within a protein, different amino acid sites evolve at different rates. Accurately modeling this variation is critical for identifying structurally or functionally important amino acid sites. Standard methods such as Rate4Site assume independent substitution rates across sites, and the most conserved ones are widely distributed in protein tertiary structure. This is biologically unrealistic because functional sites often cluster together. Here, we developed CONSTRUCT, an improved strategy for identifying functional and structurally important regions in protein tertiary structure. Given a set of orthologous sequences, CONSTRUCT first calculates site-specific substitution rates using the Rate4site model, which are then weighted by the rates of neighboring amino acid sites within a range of window sizes. The optimal window size is determined by the strongest spatial correlation, if present. This method can be analyzed using either C atoms or the center of mass of amino acid sites to account for side chain orientation. Validation on 14 functionally characterized proteins of different size, conservation level and kingdom/domain of species has demonstrated the relevance of CONSTRUCT.

bioinformatics↗

bioRxiv2024

Genomic evidence of Escherichia coli gut population diversity translocation in leukemia patients

Escherichia coli, a commensal species of the human gut, is an opportunistic pathogen which can reach extra-intestinal compartments, including the bloodstream and the bladder, among others. In non-immunosuppressed patients, purifying or neutral evolution of E. coli populations has been reported in the gut. Conversely, it has been suggested that when migrating to extra-intestinal compartments, E. coli genomes undergo diversifying selection as supported by strong evidence for adaptation. The level of genomic polymorphism and the size of the populations translocating from gut to extra-intestinal compartments is largely unknown. To gain insights in the pathophysiology of these translocations, we investigated the level of polymorphism and the evolutionary forces acting on the genomes of 77 E. coli isolated from various compartments in three immunosuppressed patients. Each patient had a unique strain which was a mutator in one case. In all instances, we observed that translocation encompasses the majority of the genomic diversity present in the gut. The same signature of selection, whether purifying or diversifying, and as anticipated, neutral for mutator isolates, was observed in both the gut and bloodstream. Additionally, we found a limited number of non-specific mutations among compartments for non-mutator isolates. In all cases, urine isolates were dominated by neutral selection. These findings indicate that substantial proportions of populations are undergoing translocation and that they present a complex compartment-specific pattern of selection at the patient level. ImportanceIt has been suggested that intra and extra-intestinal compartments differentially constrain the evolution of E. coli strains. Whether host particular conditions, such as immunosuppression, could affect the strain evolutionary trajectories remain understudied. We found that, in immunosuppressed patients, large fractions of E. coli gut populations are translocating with variable modifications of the signature of selection for commensal and pathogenic isolates according to the compartment and/or the patient. Such multiple site sampling should be performed in large cohorts of patients to get a better understanding of E. coli extra-intestinal diseases.

microbiology↗

bioRxiv2024

Escherichia coli extra-intestinal population translocation in leukemia patients

Escherichia coli, a commensal species of the human gut, is an opportunistic pathogen which can reach extra-intestinal compartments, including the bloodstream and the bladder, among others. In non-immunosuppressed patients, purifying or neutral evolution of E. coli populations has been reported in the gut. Conversely, it has been suggested that when migrating to extra-intestinal compartments, E. coli genomes undergo diversifying selection as supported by strong evidence for adaptation. The level of genomic polymorphism and the size of the populations translocating from the gut to extra-intestinal compartments is largely unknown. To gain insights in the pathophysiology of these translocations, we investigated the level of polymorphism and the evolutionary forces acting on the genomes of 77 E. coli isolated from various compartments in three immunosuppressed patients. We detected a unique strain for each patient across the blood, the urine and the gut. In one case, all isolates recovered were mutators i.e. isolates with a very high mutation rate. In all instances, we observed that translocation encompasses the majority of the genomic diversity present in the gut. The same signature of selection, whether purifying or diversifying, and as anticipated, neutral for mutator isolates, was observed in both the gut and bloodstream. Additionally, we found a limited number of non-specific mutations among compartments for non-mutator isolates. In all cases, urine isolates were dominated by neutral selection. These findings indicate that substantial proportions of populations are undergoing translocation and that they present a complex compartment-specific pattern of selection at the patient level. ImportanceIt has been suggested that intra and extra-intestinal compartments differentially constrain the evolution of E. coli strains. Whether host particular conditions, such as immunosuppression, could affect the strain evolutionary trajectories remain understudied. We found that, in immunosuppressed patients, large fractions of E. coli gut populations are translocating with variable modifications of the signature of selection for commensal and pathogenic isolates according to the compartment and/or the patient. Such multiple site sampling should be performed in large cohorts of patients to get a better understanding of E. coli extra-intestinal diseases.

microbiology↗

bioRxiv2022

Faecal carriage of ESBL-producing Escherichia coli in a remote region of Niger

ObjectiveWhole genome sequencing (WGS) of extended-spectrum {beta}-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger. MethodsStools of 383 healthy participants were collected among which 92.4% were ESBL-E. coli carriers; 90 of these ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads. ResultsMost isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome. ConclusionsMassive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.

microbiology↗

bioRxiv2019

Antibiotics and food in the American press

The emergence of antimicrobial resistant infections from food is well documented in the scientific literature but, in this kind of matter, the public opinion is an important policy driver and is vastly forged by traditional media. Here, we propose a text mining study through about 500 articles from two reference daily U.S. newspapers to assess the media coverage of this issue. Our results indicate that, since the middle of the 80s, the two journals considered here adopted a very different narrative around the issue, echoing civil society concerns in one case and the official discourse in the other.

scientific communication and education↗