Rotational-echo double resonance characterization of the effects of vancomycin on cell wall synthesis in Staphylococcus aureus.
Cross-polarization magic-angle spinning and rotational-echo double resonance 13C and 15N NMR experiments have been performed on intact cells of Staphylococcus aureus labeled with D-[1-13C]alanine and [15N]glycine or with [1-13C]glycine and L-[epsilon-15N]lysine. The cells were harvested during stationary or exponential growth conditions, the latter in media with and without the addition of vancomycin. The results of these experiments allowed the in situ determination of the relative concentrations of peptidoglycan cross-links (the number of peptide-stem D-alanines covalently linked to a pentaglycyl bridge) and bridge-links (the number of peptide-stem lysines covalently linked to a pentaglycyl bridge). The concentration of cross-links remained constant in the presence of vancomycin, whereas the number of bridge-links decreased. These changes suggest that vancomycin (at therapeutic levels) interrupts peptidoglycan synthesis in S. aureus by interference with transglycosylation.
Cegelski
Lynette
L
Department of Chemistry, Washington University, St. Louis, Missouri 63110, USA.
Kim
Sung Joon
SJ
Hing
Andrew W
AW
Studelska
Daniel R
DR
O'Connor
Robert D
RD
Mehta
Anil K
AK
Schaefer
Jacob
J
D000409:Alanine / Q000737:chemistry; D002247:Carbon Isotopes / Q000737:chemistry; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D009587:Nitrogen Isotopes / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010457:Peptidoglycan / Q000096:biosynthesis / Q000737:chemistry; D013211:Staphylococcus aureus / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development*; D014640:Vancomycin / Q000737:chemistry* / Q000494:pharmacology
D002247:Carbon Isotopes; D003432:Cross-Linking Reagents; D009587:Nitrogen Isotopes; D010457:Peptidoglycan; D014640:Vancomycin; D008239:Lysine; D000409:Alanine; D005998:Glycine