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Proteomic and transcriptomic analysis of linezolid resistance in Streptococcus pneumoniae

Jie Feng1, Dewan S Billal, Andréanne Lupien

  • 1Centre de Recherche en Infectiologie and Plate-forme §Protéomique du Centre de génomique de Québec, Université Laval, CHUQ, Pavillon CHUL, 2705 boulevard Laurier, Quebec, QC, Canada, G1V 4G2.

Journal of Proteome Research
|August 31, 2011
PubMed

Insights

Linezolid resistance in Streptococcus pneumoniae may involve increased carbohydrate metabolism and transport. Alterations in sugar metabolism proteins and transporters contribute to antibiotic resistance.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Linezolid is a crucial antibiotic for treating infections caused by Gram-positive bacteria.
  • Resistance to linezolid, though uncommon, is an emerging clinical concern.
  • Genetic mutations have been identified in linezolid-resistant Streptococcus pneumoniae.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying linezolid resistance in Streptococcus pneumoniae.
  • To identify metabolic and transport pathways affected in resistant strains.
  • To explore potential therapeutic targets for overcoming linezolid resistance.

Main Methods:

  • Comparative genomics of linezolid-resistant mutants.
  • Proteomic and transcriptomic analyses to profile gene and protein expression.
  • Functional studies involving gene disruption of specific transporters and regulators.

Main Results:

  • Linezolid-resistant S. pneumoniae mutants exhibit an upregulation of carbohydrate metabolism and transport proteins.
  • Overexpression of glycolytic enzymes and sugar transporters was observed in resistant strains.
  • Disruption of specific ABC transporters and catabolite control protein A increased linezolid susceptibility, indicating their role in resistance.

Conclusions:

  • Metabolic alterations, particularly in carbohydrate processing, are significantly associated with linezolid resistance in S. pneumoniae.
  • Targeting sugar metabolism and transport pathways could be a strategy to combat linezolid resistance.
  • This study provides a global perspective on the molecular basis of antibiotic resistance in S. pneumoniae.

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