Increase in glutamine-non-amidated muropeptides in the peptidoglycan of vancomycin-resistant Staphylococcus aureus strain Mu50.

Abstract

The peptidoglycan compositions of vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50 (MIC 8 mg/L) and hetero-VRSA strain Mu3 (MIC 3 mg/L) were compared in order to understand the mechanism of vancomycin resistance. As compared with Mu3, the cell wall of Mu50 had increased amounts of glutamine-non-amidated muropeptides and decreased cross-linking of peptidoglycan with a greatly decreased dimer/monomer ratio of muropeptides. In agreement with this observation, the peptidoglycan of Mu50 bound 1.4 times more vancomycin than that of Mu3. The increase in non-amidated muropeptides and the reduced cross-linking of the cell-wall peptidoglycan may contribute to the vancomycin resistance by increasing the consumption of vancomycin by the pre-existing cell wall of Mu50 and reducing the amount of vancomycin reaching the cytoplasmic membrane where the vital targets of the antibiotic are situated.

Antimicrobial resistance: the example of Staphylococcus aureus

“…The VISA strains are notable for the additional quantities of synthesized peptidoglycan that result in irregularly shaped, thickened cell walls. There is also decreased cross-linking of peptidoglycan strands, which leads to the exposure of more D-Ala-D-Ala residues (72,73). The altered cross-linking results from reduced amounts of L-glutamine that are available for amidation of D-glutamate in the pentapeptide bridge (70).…”

An introduction to staphylococcus aureus, and techniques for identifying and quantifying s. aureus adhesins in relation to adhesion to biomaterials: review

“…Upon exposure to vancomycin, certain MRSA strains frequently generate VISA strains, called hetero-VISA (Hiramatsu, 2001). VISA resistance appears to be associated with thickening of the cell wall peptidoglycan, and due to an increase in the target for the glycopeptide in the cell wall, therefore requiring more glycopeptide to inhibit the bacteria from growing (Hanaki et al, 1998). All VISA strains isolated appear to have a common mechanism of resistance, which differs from that found in vancomycin resistant enterococci, in that enterococcal van genes are not present (Walsh, 1993).…”

Cell Wall Thickening Is a Common Feature of Vancomycin Resistance in Staphylococcus aureus

“…Mu50 and its putative precursor strain Mu3, designated hetero-VRSA (16), have increased cell wall synthesis. When compared with vancomycin-susceptible control strains, they have enhanced incorporation of N-acetylglucosamine (GlcNAc) into the cell wall, an increased pool size of the cytoplasmic murein monomer precursor (UDP-N-acetylmuramyl-pentapeptide), an increased cell wall turnover rate as measured by the release of radiolabeled cell wall materials, and increased production of penicillin-binding proteins 2 and 2Ј (11,12,14,17). In addition to these common features with hetero-VRSA strain Mu3, VRSA strain Mu50 displays about a twofold increase in cell wall thickness, slower release of cell wall mate-rial, and an increased proportion of glutamine-nonamidated muropeptides in its cell wall (11,12).…”