Transcriptomic and functional analysis of an autolysis-deficient, teicoplanin-resistant derivative of methicillin-resistant Staphylococcus aureus.

Détails

ID Serval
serval:BIB_0BC508F2B8D4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Transcriptomic and functional analysis of an autolysis-deficient, teicoplanin-resistant derivative of methicillin-resistant Staphylococcus aureus.
Périodique
Antimicrobial Agents and Chemotherapy
Auteur⸱e⸱s
Renzoni A., Barras C., François P., Charbonnier Y., Huggler E., Garzoni C., Kelley W.L., Majcherczyk P., Schrenzel J., Lew D.P., Vaudaux P.
ISSN
0066-4804[print], 0066-4804[linking]
Statut éditorial
Publié
Date de publication
2006
Volume
50
Numéro
9
Pages
3048-3061
Langue
anglais
Résumé
The molecular basis of glycopeptide-intermediate S. aureus (GISA) isolates is not well defined though frequently involves phenotypes such as thickened cell walls and decreased autolysis. We have exploited an isogenic pair of teicoplanin-susceptible (strain MRGR3) and teicoplanin-resistant (strain 14-4) methicillin-resistant S. aureus strains for detailed transcriptomic profiling and analysis of altered autolytic properties. Strain 14-4 displayed markedly deficient Triton X-100-triggered autolysis compared to its teicoplanin-susceptible parent, although microarray analysis paradoxically did not reveal significant reductions in expression levels of major autolytic genes atl, lytM, and lytN, except for sle1, which showed a slight decrease. The most important paradox was a more-than-twofold increase in expression of the cidABC operon in 14-4 compared to MRGR3, which was correlated with decreased expression of autolysis negative regulators lytSR and lrgAB. In contrast, the autolysis-deficient phenotype of 14-4 was correlated with both increased expression of negative autolysis regulators (arlRS, mgrA, and sarA) and decreased expression of positive regulators (agr RNAII and RNAIII). Quantitative bacteriolytic assays and zymographic analysis of concentrated culture supernatants showed a striking reduction in Atl-derived, extracellular bacteriolytic hydrolase activities in 14-4 compared to MRGR3. This observed difference was independent of the source of cell wall substrate (MRGR3 or 14-4) used for analysis. Collectively, our results suggest that altered autolytic properties in 14-4 are apparently not driven by significant changes in the transcription of key autolytic effectors. Instead, our analysis points to alternate regulatory mechanisms that impact autolysis effectors which may include changes in posttranscriptional processing or export.
Mots-clé
Bacteriolysis/genetics, Cell Wall/genetics, Extracellular Fluid/enzymology, Humans, Hydrolases/metabolism, Methicillin Resistance, Octoxynol, Oligonucleotide Array Sequence Analysis, Peptide Hydrolases/biosynthesis, Peptide Hydrolases/genetics, Staphylococcus aureus/drug effects, Staphylococcus aureus/genetics, Teicoplanin/pharmacology, Transcription, Genetic
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:54
Dernière modification de la notice
20/08/2019 12:33
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