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1: Antimicrob Agents Chemother. 2007 Oct;51(10):3627-33. Epub 2007 Jul 23.
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Fluorescence ratio imaging microscopy shows decreased access of vancomycin to cell wall synthetic sites in vancomycin-resistant Staphylococcus aureus.

Pereira PM, Filipe SR, Tomasz A, Pinho MG.

Laboratory of Bacterial Cell Biology, Instituto de Tecnologia Química e Biológica, Av da Republica, 2781-901, Oeiras, Portugal.

A new method of fluorescence ratio imaging microscopy was used to compare the in vivo binding capacity and the access of a fluorescent derivative of vancomycin to the cell wall synthetic sites in isogenic pairs of vancomycin-susceptible and -resistant laboratory mutants and vancomycin-intermediate and -susceptible clinical isolates of Staphylococcus aureus. Live cells of resistant strains were found to bind approximately 1.5 times more antibiotic, but there was no correlation between the increased binding capacity and the MICs of the strains. In both susceptible and resistant bacteria, the subcellular sites of wall synthesis were localized to the division septa, but the rate of diffusion of drug molecules to these sites was reduced in resistant cells. The findings allow a reinterpretation of the mechanism of vancomycin resistance in which the path of vancomycin to its lethal target (lipid II) is considered to be through the division septum and therefore is dependent on the stage of the staphylococcal cell cycle.

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PMID: 17646417 [PubMed - indexed for MEDLINE]

PMCID: PMC2043281