title: Morphological and genetic differences in two isogenic Staphylococcus aureus strains with decreased susceptibilities to vancomycin.
abstract: Many VISA (vancomycin intermediately resistant Staphylococcus aureus) strains are characterized by increased cell wall biosynthesis and decreased cross-linking of the peptide side chains, leading to accumulation of free D-alanyl-D-alanine termini in the peptidoglycan, which act as false target sites for vancomycin. A spontaneous mutant of methicillin-resistant VISA strain SA137/93A (vancomycin MIC [E-test], 8 micro g/ml), called SA137/93G, showed increased resistance to vancomycin (MIC [E-test], 12 micro g/ml). Analysis of the resistance profile of the mutant revealed a loss of beta-lactam resistance with a concomitant increase in resistance to glycopeptides. In both strains, cell wall thickness was 1.4-fold greater than that of control isolates. However, cross-linking of the cell wall was drastically lower in SA137/93A than in SA137/93G. The sensitivity of strain SA137/93G to beta-lactams was due to loss of the beta-lactamase plasmid and a deletion that comprises 32.5 kb of the methicillin resistance cassette SCCmec, as well as 65.4 kb of chromosomal DNA. A spontaneous mutant of SA137/93G with higher sensitivity to vancomycin displayed a cell wall profile similar, in some respects, to that of an fmhB mutant. Results described here and elsewhere show that the only feature common to all VISA strains is a thickened cell wall, which may play a central role in the vancomycin resistance mechanism.
authors.affiliation: Institut für Medizinische Mikrobiologie und Immunologie, Universität Bonn, D-53105 Bonn, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Reipert
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ehlert
authors.forename: Thomas
authors.initials: T
authors.lastname: Kast
authors.forename: Gabriele
authors.initials: G
authors.lastname: Bierbaum
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects; D016521:Electrophoresis, Gel, Pulsed-Field; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin