Deregulation of the arginine deiminase (arc) operon in penicillin-tolerant mutants of Streptococcus gordonii.

Détails

ID Serval
serval:BIB_21686D759119
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Deregulation of the arginine deiminase (arc) operon in penicillin-tolerant mutants of Streptococcus gordonii.
Périodique
Antimicrobial Agents and Chemotherapy
Auteur⸱e⸱s
Caldelari I., Loeliger B., Langen H., Glauser M.P., Moreillon P.
ISSN
0066-4804 (Print)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
2000
Volume
44
Numéro
10
Pages
2802-2810
Langue
anglais
Résumé
Penicillin tolerance is an incompletely understood phenomenon that allows bacteria to resist drug-induced killing. Tolerance was studied with independent Streptococcus gordonii mutants generated by cyclic exposure to 500 times the MIC of penicillin. Parent cultures lost 4 to 5 log(10) CFU/ml of viable counts/24 h. In contrast, each of four independent mutant cultures lost < or =2 log(10) CFU/ml/24 h. The mutants had unchanged penicillin-binding proteins but contained increased amounts of two proteins with respective masses of ca. 50 and 45 kDa. One mutant (Tol1) was further characterized. The two proteins showing increased levels were homologous to the arginine deiminase and ornithine carbamoyl transferase of other gram-positive bacteria and were encoded by an operon that was >80% similar to the arginine-deiminase (arc) operon of these organisms. Partial nucleotide sequencing and insertion inactivation of the S. gordonii arc locus indicated that tolerance was not a direct consequence of arc alteration. On the other hand, genetic transformation of tolerance by Tol1 DNA always conferred arc deregulation. In nontolerant recipients, arc was repressed during exponential growth and up-regulated during postexponential growth. In tolerant transformants, arc was constitutively expressed. Tol1 DNA transformed tolerance at the same rate as transformation of a point mutation (10(-2) to 10(-3)). The tolerance mutation mapped on a specific chromosomal fragment but was physically distant from arc. Importantly, arc deregulation was observed in most (6 of 10) of additional independent penicillin-tolerant mutants. Thus, although not exclusive, the association between arc deregulation and tolerance was not fortuitous. Since penicillin selection mimicked the antibiotic pressure operating in the clinical environment, arc deregulation might be an important correlate of naturally occurring tolerance and help in understanding the mechanism(s) underlying this clinically problematic phenotype.
Mots-clé
Amino Acids/analysis, Bacterial Outer Membrane Proteins/genetics, Chromosome Mapping, Chromosomes, Bacterial/genetics, DNA, Bacterial/analysis, DNA, Bacterial/genetics, Electrophoresis, Polyacrylamide Gel, Escherichia coli Proteins, Gene Expression Regulation, Bacterial/genetics, Gene Expression Regulation, Enzymologic/genetics, Hydrolases/genetics, Luciferases/genetics, Membrane Proteins/genetics, Microbial Sensitivity Tests, Molecular Sequence Data, Mutation/genetics, Operon/genetics, Penicillin Resistance/genetics, Protein Kinases/genetics, Repressor Proteins, Streptococcus/enzymology, Streptococcus/genetics, Time Factors, Transformation, Genetic/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:58
Dernière modification de la notice
20/08/2019 12:58
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