Lysostaphin

This chapter describes the structural chemistry and the biological aspects of lysostaphin. Lysostaphin has been tested as a novel antistaphylococcal agent and as a reagent for typing staphylococci. One of its more important functions, however, is in the research laboratory where it is frequently used to lyse staphylococcal cell walls for the liberation of intracellular enzymes, nucleic acids, and cell membrane and surface components. The importance of lysostaphin in staphylococci-related studies is underlined by the fact that many staphylococci are resistant to conventional lysis methods. Lysostaphin cleaves staphylococcal peptidoglycans in general but is directed specifically to Staphylococcus aureus target cells. In lysing staphylococci, the key enzymatic reaction of lysostaphin is the specific cleavage of the Gly–Gly bond in the pentaglycine subunit of the cell wall peptidoglycan. Lysostaphin is synthesized as a preproenzyme of M_r 42,000 with a signal peptide that is cleaved intracellularly and an N-terminal propeptide removed extracellularly to yield a mature 27 kDa enzyme. The sequence element that is responsible for binding to the cell wall of Staphylococcus aureus is at the C-terminus of the molecule.