Titre
A single mutation in enzyme I of the sugar phosphotransferase system confers penicillin tolerance to Streptococcus gordonii.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Bizzini, A.
Auteure/Auteur
Entenza, J.M.
Auteure/Auteur
Michielin, O.
Auteure/Auteur
Arnold, I.
Auteure/Auteur
Erni, B.
Auteure/Auteur
Moreillon, P.
Auteure/Auteur
Liens vers les personnes
ISSN
1098-6596
Statut éditorial
Publié
Date de publication
2010
Volume
54
Numéro
1
Première page
259
Dernière page/numéro d’article
266
Langue
anglais
Résumé
Tolerance is a poorly understood phenomenon that allows bacteria exposed to a bactericidal antibiotic to stop their growth and withstand drug-induced killing. This survival ability has been implicated in antibiotic treatment failures. Here, we describe a single nucleotide mutation (tol1) in a tolerant Streptococcus gordonii strain (Tol1) that is sufficient to provide tolerance in vitro and in vivo. It induces a proline-to-arginine substitution (P483R) in the homodimerization interface of enzyme I of the sugar phosphotransferase system, resulting in diminished sugar uptake. In vitro, the susceptible wild-type (WT) and Tol1 cultures lost 4.5 and 0.6 log(10) CFU/ml, respectively, after 24 h of penicillin exposure. The introduction of tol1 into the WT (WT P483R) conferred tolerance (a loss of 0.7 log(10) CFU/ml/24 h), whereas restitution of the parent sequence in Tol1 (Tol1 R483P) restored antibiotic susceptibility. Moreover, penicillin treatment of rats in an experimental model of endocarditis showed a complete inversion in the outcome, with a failure of therapy in rats infected with WT P483R and the complete disappearance of bacteria in animals infected with Tol1 R483P.
Sujets
PID Serval
serval:BIB_1D1C379268F2
PMID
Open Access
Oui
Date de création
2010-01-08T13:44:45.988Z
Date de création dans IRIS
2025-05-20T13:24:08Z