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ramR deletion in an Enterobacter hormaechei isolate as a consequence of therapeutic failure to key antibiotics in a long-term hospitalized patient

Abstract : Genome changes are central to the adaptation of bacteria especially under antibiotic pressure. The aim of this study was to report phenotypic and genomic adaptation undergone by Enterobacter hormaechei clinical strain that became highly resistant to key antimicrobials during a four months period in a patient hospitalized in intensive care unit (ICU). All six clinical E. hormaechei strains isolated in one ICU-hospitalized patient have been studied. MICs regarding 17 antimicrobial molecules have been measured. Single nucleotide polymorphism (SNP), was determined on the sequenced genomes. The expression of genes involved in antibiotic resistance among Enterobacter cloacae complex strains were determined by qRT-PCR. All the strains belonging to the same Sequence-Type 66 and were distant by a maximum of nine SNP. After three months of hospitalization, three strains presented a significant increase in MICs regarding ceftazidime, cefepime, temocillin, ertapenem, tigecycline, ciprofloxacin and chloramphenicol. Those resistant strains did not acquire additional antibiotics resistant genes but harbored a 16 bp deletion in the ramR gene. This deletion led to the up expression of RamA, AcrA, AcrB, TolC and the down expression of OmpF. The ΔramR mutant harbored the same phenotype as the resistant clinical strains regarding tigecycline, chloramphenicol and ciprofloxacin. The increased expression of RamA due to partial deletion in the ramR gene led to a cross resistance phenotype by an increase of antibiotics efflux through the AcrAB-TolC pump and the decrease of antibiotics permeability by porin OmpF. ramR appears to be an important adaptative trait for E. hormachei strains.
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https://hal.archives-ouvertes.fr/hal-02930671
Contributor : Laurent Jonchère <>
Submitted on : Friday, September 11, 2020 - 2:43:39 PM
Last modification on : Tuesday, September 15, 2020 - 4:49:19 PM

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François Gravey, Vincent Cattoir, Frédéric Ethuin, Laëtitia Fabre, Racha Beyrouthy, et al.. ramR deletion in an Enterobacter hormaechei isolate as a consequence of therapeutic failure to key antibiotics in a long-term hospitalized patient. Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2020, ⟨10.1128/AAC.00962-20⟩. ⟨hal-02930671⟩

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