Factors influencing methicillin resistance in staphylococci.
Methicillin resistance in staphylococci is due to an acquired penicillin-binding protein, PBP2' (PBP2a). This additional PBP, encoded by mecA, confers an intrinsic resistance to all beta-lactams and their derivatives. Resistance levels in methicillin-resistant Staphylococcus aureus (MRSA) depend on efficient PBP2' production and are modulated by chromosomal factors. Depending on the genetic background of the strain that acquired mecA, resistance levels range from phenotypically susceptible to highly resistant. Characteristic for most MRSA is the heterogeneous expression of resistance, which is due to the segregation of a more highly resistant subpopulation upon challenge with methicillin. Maximal expression of resistance by PBP2' requires the efficient and correct synthesis of the peptidoglycan precursor. Genes involved in cell-wall precursor formation and turnover, regulation, transport, and signal transduction may determine the level of resistance that is expressed. At this stage, however, there is no information available on the functionality or efficacy of such factors in clinical isolates in relation to methicillin resistance levels.
Institute of Medical Microbiology, University of Zürich, Gloriastrasse 32, PO Box, 8028 Zürich, Switzerland. bberger@immv.unizh.ch
Brigitte
B
Berger-Bächi
Susanne
S
Rohrer
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006602:Hexosyltransferases; D006801:Humans; D016106:Methicillin Resistance / Q000235:genetics; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects*
D001426:Bacterial Proteins; D002352:Carrier Proteins; C101640:MecI protein, Staphylococcus; D046915:Penicillin-Binding Proteins; D012097:Repressor Proteins; C101641:mecR1 protein, Staphylococcus aureus; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase