Figure 4. Cytolysin is expressed and processed through a complex maturation pathway (64). The cytolysin precursors, CylL_L and CylL_S, are ribosomally synthesized. The putative modification protein, CylM, is required for the expression of CylL_L and CylL_S in an activatable form, and the secreted forms, CylL_L and CylL_S were recently shown to possess the amino acid lanthionine as the result of posttranslational modification (64). CylL_L and CylL_S both are secreted by CylB (65), which is accompanied by an initial proteolytic trimming event (64) converting each to CylL_L' and CylL_S', respectively. Once secreted, CylL_L' and CylL_S' are both functionally inactive until six amino acids are removed from each amino terminus. This final step in maturation is catalyzed by CylA (64), a subtilisin-type serine protease. Since this final catalytic event is essential, occurs extracellularly, and is catalyzed by a class of enzyme for which a substantial body of structural information exists, it represents an ideal therapeutic target. As shown in Figure 3, inhibition of cytolysin by mutation (or potentially by therapeutic intervention) results in a reduction by several orders of magnitude in the number of circulating organisms.