The pneumococcal cell wall degrading enzymes: A modular design to create new lysins?

Autolysins are enzymes that degrade different bonds in the peptidoglycan and, eventually, cause the lysis and death of the cell, Streptococcus pneumoniae contains a powerful autolytic enzyme that has been characterized as an N-acetylmuramoyl-L-alanine amidase, We have cloned the lytA gene coding for this amidase and studied in depth the genetics and expression of this gene, which represented the first molecular analysis of a bacterial autolysin, Two observations have been fundamental in revealing further knowledge on the lytic systems of pneumococcus: (a) The well-documented dependence of the pneumococcal autolysin on the presence of choline in the cell wall for activity, and (b) the early observation that Most pneumococcal phages also required the presence of this amino-alcohol in the growth medium to achieve a successful liberation of the phage progeny, We concluded that choline would serve as an element of strong selective pressure to preserve certain structures of the host and phage lytic enzymes which should lead to sequence homologies, We constructed active chimeras between the lytic enzymes of S. pneumoniae and its bacteriophages using genes that share sequence homology as well as genes that completely lack homologous regions, In this way, we demonstrated that the pneumococcal lytic enzymes are the result of the fusion of two independent functional modules where the carboxy-terminal domain might be responsible for the specific recognition of choline-containing cell, walls whereas the active center of these enzymes should be localized in the N-terminal part of the protein, The modular design postulated for the pneumococcal ly sins seems to be a widespread model for many types of microbial proteins and the construction of functional chimeric proteins between the lytic enzymes of pneumococcus and those of several gram-positive microorganisms, like Clostridium acetobutylicum or Lactococcus lactis, provided interesting clues on the modular evolution of proteins, The study of several genes coding for the lytic enzymes of temperate phages of pneumococcus also highlighted on some evolutionary relationships between microorganisms, We suggest that lysogenic relationships may represent a common mechanism by which pathogenic organisms like pneumococcus should undergo a rapid adaptation to an evolving environment.