Journal of Antimicrobial Chemotherapy, Vol 42, 199-209, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
H Hanaki, K Kuwahara-Arai, S Boyle-Vavra, RS Daum, H Labischinski and K Hiramatsu
We have previously reported methicillin-resistant Staphylococcus aureus
clinical strains, Mu50 and Mu3, representing two categories of vancomycin
resistance: Mu50 representing vancomycin-resistant S. aureus (VRSA) with
MICs > or = 8 mg/L, and Mu3 representing hetero-VRSA with MICs < or =
4 mg/L using standard MIC determination methods. The mechanisms of
vancomycin resistance in these strains were investigated. These strains did
not carry the enterococcal vancomycin-resistance genes, vanA, vanB, or
vanC1-3, as tested by PCR using specific primers. However, both strains
produced three to five times the amount of penicillin-binding proteins
(PBPs) 2 and 2' when compared with vancomycin-susceptible S. aureus control
strains with or without methicillin resistance; the amounts of PBP2
produced in Mu3 and Mu50 were comparable to those in the
vancomycin-resistant S. aureus mutant strains selected in vitro.
Incorporation of 14C-labelled Nacetyl- glucosamine into the cell was three
to 20 times increased in Mu50 and Mu3, and release of the radioactive cell
wall material was increased in Mu3 (and also in Mu50, though to a lesser
extent), compared with control strains. The amounts of intracellular murein
monomer precursor in these strains were three to eight times greater than
those found in control strains. Transmission electron microscopy showed a
doubling in the cell wall thickness in Mu50 compared with the control
strains. Mu3 did not show obvious cell wall thickening. These data indicate
that activated synthesis and an increased rate of cell wall turnover are
common features of Mu3 and Mu50 and may be the prerequisite for the
expression of vancomycin resistance in S. aureus.
ORIGINAL ARTICLES
Activated cell-wall synthesis is associated with vancomycin resistance in methicillin-resistant Staphylococcus aureus clinical strains Mu3 and Mu50
Department of Bacteriology, Juntendo University, Tokyo, Japan.
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