Modification of peptidoglycan precursors is a common feature of the low-level vancomycin-resistant VANB-type Enterococcus D366 and of the naturally glycopeptide-resistant species Lactobacillus casei, Pediococcus pentosaceus, Leuconostoc mesenteroides, and Enterococcus gallinarum.
The biochemical basis for the acquired or natural resistance of various gram-positive organisms to glycopeptides was studied by high-pressure liquid chromatographic analysis of their peptidoglycan UDP-MurNAc-peptide precursors. In all cases, resistance was correlated with partial or complete replacement of the C-terminal D-Ala-D-Ala-containing UDP-MurNAc-pentapeptide by a new precursor with a modified C terminus. Nuclear magnetic resonance analysis by sequential assignment showed that the new precursor encountered in Enterococcus faecium D366, a strain belonging to the VANB class, which expresses low-level resistance to vancomycin, was UDP-MurNAc-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-lactate, identical to that previously found in the VANA class, which expresses high-level resistance to vancomycin. High-pressure liquid chromatographic analyses, composition determinations, and digestion by R39 D,D-carboxypeptidase demonstrated the exclusive presence of the new precursor in Lactobacillus casei and Pediococcus pentosaceus, which are naturally highly resistant to glycopeptides. The low-level natural resistance of Enterococcus gallinarum to vancomycin was found to be associated with the synthesis of a new precursor identified as a UDP-MurNAc-pentapeptide containing a C-terminal D-serine. The distinction between low and high levels of resistance to glycopeptides appeared also to depend on the presence or absence of a substantial residual pool of a D-Ala-D-Ala-containing UDP-MurNAc-pentapeptide.
Billot-Klein
D
D
Laboratoire de RMN, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Gutmann
L
L
Sablé
S
S
Guittet
E
E
van Heijenoort
J
J
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004352:Drug Resistance, Microbial; D006094:Gram-Positive Bacteria / Q000737:chemistry* / Q000187:drug effects*; D007780:Lacticaseibacillus casei / Q000737:chemistry / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000737:chemistry*; D013289:Streptococcaceae / Q000737:chemistry / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D010457:Peptidoglycan; D014640:Vancomycin