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Semi-Quantitative Analysis of Peptidoglycan by Liquid Chromatography Mass Spectrometry and Bioinformatics
09:09

Semi-Quantitative Analysis of Peptidoglycan by Liquid Chromatography Mass Spectrometry and Bioinformatics

Published on: October 13, 2020

The carboxyl terminus of peptidoglycan stem peptides is a determinant for methicillin resistance in Staphylococcus

Boudewijn L M De Jonge1, Douglas Gage, Naxing Xu

  • 1Laboratory of Microbiology, The Rockefeller University, New York, New York 10021, USA. boudewijn.dejonge@astrazeneca.com

Antimicrobial Agents and Chemotherapy
|September 18, 2002
PubMed

Insights

High concentrations of D-amino acids like D-serine in Staphylococcus aureus growth media can replace key components of its cell wall, reducing resistance to methicillin (a common antibiotic). This impacts bacterial antibiotic resistance mechanisms.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antibiotic Resistance Research

Background:

  • Staphylococcus aureus is a significant pathogen known for developing antibiotic resistance.
  • The mecA gene confers resistance to methicillin by altering penicillin-binding proteins.
  • Peptidoglycan biosynthesis is a crucial target for antibiotics like methicillin.

Purpose of the Study:

  • To investigate the impact of exogenous D-amino acids on Staphylococcus aureus cell wall synthesis.
  • To determine how D-amino acid incorporation affects methicillin resistance in mecA-positive strains.
  • To explore potential interactions between mecA-mediated resistance and alternative peptidoglycan precursors.

Main Methods:

  • Culturing a mecA-containing Staphylococcus aureus strain in media supplemented with high concentrations of D-serine, D-threonine, or D-phenylalanine.
  • Analyzing the peptidoglycan stem peptides to identify alterations in the carboxyl-terminal D-alanine residue.
  • Assessing the growth of these modified strains in the presence of varying concentrations of methicillin.

Main Results:

  • Incorporation of exogenous D-amino acids (D-serine, D-threonine, D-phenylalanine) into peptidoglycan stem peptides was observed, replacing the native D-alanine.
  • This replacement led to a significant reduction in the ability of Staphylococcus aureus to grow in the presence of methicillin, with D-serine showing the most pronounced effect.
  • Strains grown with 32 mM D-serine exhibited a drastic decrease in methicillin tolerance, from 800 µg/ml to less than 50 µg/ml.

Conclusions:

  • The study demonstrates that altering peptidoglycan stem peptide composition by incorporating exogenous D-amino acids can compromise methicillin resistance in Staphylococcus aureus.
  • These findings suggest that vancomycin resistance mechanisms in S. aureus, which involve alternative precursors, may be mutually exclusive with the expression of mecA-mediated methicillin resistance.
  • Targeting cell wall biosynthesis pathways with alternative D-amino acids presents a potential strategy to overcome antibiotic resistance in S. aureus.

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