Carbapenemase-producing Enterobacteriaceae (CPE) are classified as emerging Highly Resistant Bacteria (eHRB) because they expose infected patients to the risk of treatment failure due to the strains' resistance to last-line β-lactams, carbapenems, and frequent co-resistance to other classes of antibiotics, leading to increased morbidity and mortality. Their high epidemiogenic potential has enabled their global spread. In France, the incidence of Carbapenemase-producing Enterobacteriaceae is rising sharply, both in colonization and in infections. Parallel to this increase, Escherichia coli has become the most common Carbapenemase-producing Enterobacteriaceae (35% of strains in 2024, National Research Committee data), surpassing Klebsiella pneumoniae (24%).
The investigators hypothesize that the increase in the prevalence of carbapenemase-producing Echerichia coli is associated with a diversification of clones, enzymes, and their variants, and may pose a threefold threat: i) the spread of genes encoding carbapenemases within pathogenic extraintestinal Echerichia coli (ExPEC) pathogroups responsible for urinary tract infections and bacteremias, with a high risk of resistance spreading in the community, ii) the silent spread of Echerichia coli strains producing OXA-48 variants with reduced carbapenem hydrolytic activity, OXA-244 and OXA-484, which are not detected or poorly detected by conventionally used screening media and iii) the emergence of New Dehli Metallo-beta-lactamase (NDM) variants with high hydrolytic activity, such as NDM-5, within Echerichia coli clones possessing Penicillin-Binding Proteins (PLPs) with low affinity for antibiotics, leading to very high-level resistance and a therapeutic dead end in infected patients.
Not applicable to this study of an existing collection of Carbapenemase-producing Enterobacteriaceae strains.
Not applicable to this study of an existing collection of Carbapenemase-producing Enterobacteriaceae strains.
This translational research study involves the analysis of samples from an existing multicenter cohort: the strain bank of the Reference Laboratory for Medical Biology (LBMR) for Emerging Highly Resistant Bacteria (eHRB). It is a collection of 163 carbapenemase-producing E. coli strains collected at the Microbiology Laboratory between 2023 and 2024. The panel of E. coli strains isolated from various infections and colonization sites will be selected following genomic characterization to ensure it is as representative as possible of the predominant clones identified. The selected strains will then be phenotypically characterized through further analyses.
Cohort
Prospective
MultiLocus Sequence Typing
GeneticStudy of the genetic diversity of carbapenemase-producing E. coli strains from the Reference Laboratory for Medical Biology (LBMR) for Emerging Highly Resistant Bacteria (eHRB) via whole-genome sequencing of bacterial genomes and analysis using whole-genome MultiLocus Sequence Typing (wgMLST) to characterize the molecular epidemiology and identify high-risk clones circulating in southern France and assessment of the content of antibiotic resistance genes (resistome), virulence genes (virulome), and plasmids (percentage of presence).
Genetic diversity of carbapenemase-producing E. coli strains from the Reference Laboratory for Medical Biology for Emerging Highly Resistant Bacteria
Typing via whole-genome sequencing of bacterial genomes and analysis using whole-genome MultiLocus Sequence Typing (wgMLST) to characterize the molecular epidemiology and identify high-risk clones circulating in southern France
Assessment of the content of antibiotic resistance genes (resistome), virulence genes (virulome), and plasmids (percentage of presence).
Resistome, virulome and plasmids will be measured as percentages in each strain identified.
Antibiotic resistance phenotype:
Antibiotic susceptibility testing on Mueller-Hinton agar plates with determination of Minimum Inhibitory Concentrations (MICs) of last-line antibiotics in liquid Mueller-Hinton medium
Study of bacterial growth curves for the main identified clones
Growth curves will be compared using the Gompertz nonlinear regression model with GraphPad Prism 9.2 software (San Diego, CA, USA).
Study of biofilm formation (Bioflux 200TM system) for the main identified clones,
The Bioflux 200TM system will be used to study biofilm formation
Study of bacterial motility (swimming, swarming) for the main identified clones
The motility of the different bacterial strains will be assessed by comparing the average migration diameters for swimming and swarming. The experiments will be conducted independently three times.
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