The carboxyl terminus of peptidoglycan stem peptides is a determinant for methicillin resistance in Staphylococcus aureus.
A mecA-containing Staphylococcus aureus strain was grown in the presence of high concentrations of D-serine, D-threonine, and D-phenylalanine. These growth conditions resulted in the replacement of the carboxyl-terminal (fifth) D-alanine residue of peptidoglycan stem peptides with the D-amino acid present in the growth medium and a reduced ability to grow in the presence of methicillin. The most dramatic effect was seen with D-serine. With 32 mM D-serine, strains that had been able to grow in the presence of 800 micro g of methicillin per ml were only able to grow in the presence of less than 50 micro g/ml. The results also suggest that in S. aureus vancomycin resistance mediated through the incorporation of precursors not terminating in D-alanyl-D-alanine would be mutually exclusive with expression of mecA-mediated methicillin resistance.
De Jonge
Boudewijn L M
BL
Laboratory of Microbiology, The Rockefeller University, New York, New York 10021, USA. boudewijn.dejonge@astrazeneca.com
Gage
Douglas
D
Xu
Naxing
N
D000596:Amino Acids / Q000032:analysis; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media / Q000737:chemistry; D006602:Hexosyltransferases; D013058:Mass Spectrometry; D008712:Methicillin / Q000378:metabolism; D016106:Methicillin Resistance; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010455:Peptides / Q000032:analysis*; D010457:Peptidoglycan / Q000737:chemistry*; D010458:Peptidyl Transferases; D012694:Serine / Q000378:metabolism; D013211:Staphylococcus aureus / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development; D013912:Threonine / Q000378:metabolism
D000596:Amino Acids; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003470:Culture Media; D046915:Penicillin-Binding Proteins; D010455:Peptides; D010457:Peptidoglycan; D013912:Threonine; D012694:Serine; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D008712:Methicillin