Methicillin resistance in Staphylococcus aureus: mechanisms and modulation

Sci Prog. 2002;85(Pt 1):57-72. doi: 10.3184/003685002783238870.

Abstract

Staphylococcus aureus is a major pathogen both within hospitals and in the community. Methicillin, a beta-lactam antibiotic, acts by inhibiting penicillin-binding proteins (PBPs) that are involved in the synthesis of peptidoglycan, an essential mesh-like polymer that surrounds the cell. S. aureus can become resistant to methicillin and other beta-lactam antibiotics through the expression of a foreign PBP, PBP2a, that is resistant to the action of methicillin but which can perform the functions of the host PBPs. Methicillin-resistant S. aureus isolates are often resistant to other classes of antibiotics (through different mechanisms) making treatment options limited, and this has led to the search for new compounds active against these strains. An understanding of the mechanism of methicillin resistance has led to the discovery of accessory factors that influence the level and nature of methicillin resistance. Accessory factors, such as Fem factors, provide possible new targets, while compounds that modulate methicillin resistance such as epicatechin gallate, derived from green tea, and corilagin, provide possible lead compounds for development of inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacterial Proteins*
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / drug effects
  • Carrier Proteins / genetics
  • Gene Expression Regulation, Bacterial
  • Hexosyltransferases*
  • Methicillin / pharmacology*
  • Methicillin Resistance*
  • Muramoylpentapeptide Carboxypeptidase / biosynthesis
  • Muramoylpentapeptide Carboxypeptidase / drug effects
  • Muramoylpentapeptide Carboxypeptidase / genetics
  • Penicillin-Binding Proteins
  • Penicillins / pharmacology*
  • Peptidyl Transferases*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics*

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Penicillin-Binding Proteins
  • Penicillins
  • Peptidyl Transferases
  • Hexosyltransferases
  • Muramoylpentapeptide Carboxypeptidase
  • Methicillin