ABSTRACT
Bacteriophage lytic enzymes or lysins are highly evolved molecules that have been specifically developed by phages over millions of years to quickly and efficiently allow their progeny to be released from the host bacterium. These enzymes damage the cell wall’s integrity by hydrolyzing the four major bonds in its peptidoglycan component; they include (i) endo-b-N-acetylglucosaminidases or N-acetylmuramidases (lysozymes), which act on the sugar moieties, (ii) endopeptidases, which act
on the peptide cross bridge, and (iii) N-acetylmuramyl-L-alanine amidases (or amidases), which hydrolyze the amide bond connecting the sugar and peptide moieties (Young, 1992). Most of the lysins that have been characterized thus far are amidases; the reason for this is currently unclear. The lysins usually do not have signal sequences to translocate them through the cytoplasmic membrane and cleave their substrate in the peptidoglycan. Instead, the lysins’ translocation is controlled by a second phage gene product, the holin (Wang et al., 2000). During phage development in the infected bacterium, lysin accumulates in the cytoplasm in anticipation of phage maturation. At a genetically specified time, patches of holin molecules inserted in the cytoplasmic membrane are activated, resulting in the formation of pores allowing the preformed lysin in the cytoplasm to access the peptidoglycan, there-by causing cell lysis and the release of progeny phages (Wang et al., 2000). The ability of phages to lyse their targeted bacterial hosts has been known for almost a century, and phages have been used to prevent and treat human and animal diseases of bacterial origin since the late 1910s (see Chapters 13 and 14 for more details on this subject). However, phage-encoded enzymes have only recently begun to be used for various practical applications; e.g., (i) the preparation of bacterial “ghost” vaccines (Szostak et al., 1990; 1996), and (ii) reducing bacterial contamination in dairy products (Gaeng et al., 2000). Also, the emergence of antibiotic-resistance has prompted studies to determine the efficacy of phage-encoded enzymes for the prophylaxis and treatment of bacterial diseases of humans.
