Mutations in penicillin-binding protein (PBP) genes and in non-PBP genes during selection of penicillin-resistant Streptococcus gordonii.

Détails

ID Serval
serval:BIB_B0D576EFE70E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Mutations in penicillin-binding protein (PBP) genes and in non-PBP genes during selection of penicillin-resistant Streptococcus gordonii.
Périodique
Antimicrobial Agents and Chemotherapy
Auteur(s)
Haenni M., Moreillon P.
ISSN
0066-4804[print], 0066-4804[linking]
Statut éditorial
Publié
Date de publication
2006
Volume
50
Numéro
12
Pages
4053-4061
Langue
anglais
Résumé
Penicillin resistance in Streptococcus spp. involves multiple mutations in both penicillin-binding proteins (PBPs) and non-PBP genes. Here, we studied the development of penicillin resistance in the oral commensal Streptococcus gordonii. Cyclic exposure of bacteria to twofold-increasing penicillin concentrations selected for a progressive 250- to 500-fold MIC increase (from 0.008 to between 2 and 4 microg/ml). The major MIC increase (> or = 35-fold) was related to non-PBP mutations, whereas PBP mutations accounted only for a 4- to 8-fold additional increase. PBP mutations occurred in class B PBPs 2X and 2B, which carry a transpeptidase domain, but not in class A PBP 1A, 1B, or 2A, which carry an additional transglycosylase domain. Therefore, we tested whether inactivation of class A PBPs affected resistance development in spite of the absence of mutations. Deletion of PBP 1A or 2A profoundly slowed down resistance development but only moderately affected resistance in already highly resistant mutants (MIC = 2 to 4 microg/ml). Thus, class A PBPs might facilitate early development of resistance by stabilizing penicillin-altered peptidoglycan via transglycosylation, whereas they might be less indispensable in highly resistant mutants which have reestablished a penicillin-insensitive cell wall-building machinery. The contribution of PBP and non-PBP mutations alone could be individualized in DNA transformation. Both PBP and non-PBP mutations conferred some level of intrinsic resistance, but combining the mutations synergized them to ensure high-level resistance (> or = 2 microg/ml). The results underline the complexity of penicillin resistance development and suggest that inhibition of transglycosylase might be an as yet underestimated way to interfere with early resistance development.
Mots-clé
Genes, Bacterial, Microbial Sensitivity Tests, Mutation, Penicillin Resistance/genetics, Penicillin-Binding Proteins/genetics, Selection, Genetic, Streptococcus/classification, Streptococcus/drug effects, Transformation, Genetic
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:58
Dernière modification de la notice
20/08/2019 15:19
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