A new mechanism to render clinical isolates of Escherichia coli non-susceptible to imipenem: substitutions in the PBP2 penicillin-binding domain

Abstract : Objectives: So far, two types of mechanism are known to be involved in carbapenem non-susceptibility of Escherichia coli clinical isolates: reduced outer membrane permeability associated with production of ESBLs and/or overproduction of class C beta-lactamases; and production of carbapenemases. Non-susceptibility to only imipenem observed in two clinical isolates suggested a new mechanism, described in the present study. Methods: The ST was determined for the two isolates of E. coli (strains LSNy and VSBj), and their chromosomal region encoding the penicillin-binding domain of PBP2 was amplified, sequenced and then used for recombination experiments in E. coli K12 C600. Antibiotic MICs were determined using the Etest method. Results: Strains LSNy and VSBj, which displayed ST23 and ST345, respectively, showed amino acid substitutions in their PBP2 penicillin-binding domain. Substitution Ala388Ser located in motif 2 (SXD) was common to the two strains. Two additional substitutions (Ala488Thr and Leu573Val) located outside the two other motifs were identified in strain LSNy, whereas another one (Thr331Pro) located in motif 1 was identified in strain VSBj. Recombination experiments to reproduce non-susceptibility to imipenem in E. coli K12 C600 were not successful when only the common substitution was transferred, whereas recombination with DNA fragments including either the three substitutions (strain LSNy) or the two substitutions (strain VSBj) were successful. Conclusions: Substitution of amino acids in the penicillin-binding domain of PBP2 is a new mechanism by which E. coli clinical isolates specifically resist imipenem.
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Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2016, 71 (1), pp.76 - 79. 〈https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkv318〉. 〈10.1093/jac/dkv318〉
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Soumis le : mardi 14 mars 2017 - 10:06:55
Dernière modification le : jeudi 29 novembre 2018 - 16:08:47

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Nejla Aissa, Noémie Mayer, Fréderic Bert, Roger Labia, Alain Lozniewski, et al.. A new mechanism to render clinical isolates of Escherichia coli non-susceptible to imipenem: substitutions in the PBP2 penicillin-binding domain. Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2016, 71 (1), pp.76 - 79. 〈https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkv318〉. 〈10.1093/jac/dkv318〉. 〈hal-01488973〉

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