JAC 49/2 pp. 255-260

Staphylococcus aureus has long been recognized as a major cause of hospital-acquired infection. Over the last decade, methicillin-resistant S. aureus (MRSA) strains have become endemic in hospitals worldwide, including in the UK. Accordingly, the frequency of MRSA isolation has increased dramatically. Glycopeptides, such as vancomycin, are often the therapeutic drugs of choice for serious MRSA infections. However, failures of vancomycin therapy against S. aureus, due to the emergence of strains that are significantly less susceptible to vancomycin [vancomycinresistant S. aureus (VRSA)], are now well established. The first clinical VRSA, Mu50, was isolated in Japan in 1997. The VRSA phenotype of Mu50 is the result of changes to the cell wall structure. In comparison with MRSA strains, Mu50 and Mu50-like strains have a thickened cell wall, release more cell wall material into the culture medium and have increased rates of autolysis. The fine structure of the Mu50 cell wall is similar to that of an MRSA strain such as N315, except that the Mu50 peptidoglycan chains show significantly less cross-linking, and an increased content of pentapeptide chains. The amount of glutamine-non-amidated muropeptide subunits (i.e. those containing D-glutamate rather than D-glutamine) in the Mu50 cell wall increases, and it has been proposed that the reason for decreased cross-linking is that non-amidated muropeptides are poorer substrates for transpeptidases than amidated ones, although this is yet to be confirmed. It is believed that the reason such changes in cell wall thickness and cross-linking result in vancomycin resistance is that the modified cell wall binds more vancomycin, due to the increased amount of terminal D-alanyl-D-alanine dipeptide. To understand the mechanism of vancomycin resistance in VRSA strains, it is obviously necessary first to understand how these microbes synthesize peptidoglycan.