en
Scientific article
English

Increased uptake and improved intracellular survival of a teicoplanin-resistant mutant of methicillin-resistant Staphylococcus aureus in non-professional phagocytes

Published inChemotherapy, vol. 55, no. 3, p. 183-188
Publication date2009
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
Citation (ISO format)
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
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ISSN of the journal0009-3157
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