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Increased uptake and improved intracellular survival of a teicoplanin-resistant mutant of methicillin-resistant Staphylococcus aureus in non-professional phagocytes
|Published in||Chemotherapy. 2009, vol. 55, no. 3, p. 183-188|
|Abstract||BACKGROUND/AIMS: Endogenous development of glycopeptide-intermediate resistance is linked to multiple genetic and phenotypic changes in clinical and laboratory isolates of Staphylococcus aureus. This study evaluated endocytic uptake and intracellular survival of a teicoplanin-resistant derivative of S. aureus in a human epithelial cell line, and compared these to the isogenic teicoplanin-susceptible parent or a spontaneously derived, susceptible revertant. METHODS: Endocytic uptake of teicoplanin-resistant and teicoplanin-susceptible strains by human embryonic kidney 293 cells was estimated by a lysostaphin protection assay. Differential intracellular survival of all S. aureus strains from 2 to 24 h was evaluated by colony-forming unit counts of Triton X-100-lysed 293 cells, following lysostaphin inactivation. RESULTS: Endocytic uptake of the teicoplanin-resistant strain increased by approximately 4-fold over its teicoplanin-susceptible counterparts. Furthermore, the teicoplanin-resistant strain showed an 11-fold increase in intracellular colony-forming unit counts from 2 to 24 h, compared to its teicoplanin-susceptible counterparts that showed marginal (<2-fold) changes during the same time period. Infected host cells showed no significant viability loss at 24 h, as assessed by Trypan blue dye exclusion. CONCLUSIONS: Intracellular location might confer a significant fitness benefit to glycopeptide-intermediate isolates of methicillin-resistant S. aureus and further protect them from cell wall-active antibiotics whose intracellular activity is limited.|
|Keywords||Anti-Bacterial Agents/ pharmacology — Cell Line — Drug Resistance, Bacterial — Humans — Lysostaphin/metabolism — Methicillin-Resistant Staphylococcus aureus/ drug effects/genetics/isolation & — Purification — Microbial Sensitivity Tests — Mutation — Phagocytes/ microbiology — Teicoplanin/ pharmacology — Time Factors|
|Research group||Acquisition et expression de facteurs de virulence chez Staphylococcus aureus (86)|
|RENZONI, Adriana Maria et al. Increased uptake and improved intracellular survival of a teicoplanin-resistant mutant of methicillin-resistant Staphylococcus aureus in non-professional phagocytes. In: Chemotherapy, 2009, vol. 55, n° 3, p. 183-188. doi: 10.1159/000215304 https://archive-ouverte.unige.ch/unige:7545|