Lysin

Lysin is a term used in microbiology to describe enzymes that cause lysis of bacterial cells by degrading peptidoglycan in the cell wall. Most lysins are endolysins encoded by bacteriophages, produced near the end of the lytic cycle to rupture the host cell and release newly formed phage particles. Some bacteria also produce lysins as autolytic enzymes.

Mechanism and architecture: Lysins are peptidoglycan hydrolases that cleave specific bonds within the bacterial cell wall. Many lysins have a modular architecture with an N-terminal catalytic domain and a C-terminal cell-wall binding domain; catalytic domains can be amidases, glycosidases, or endopeptidases, among others. The CBD determines the host range by recognizing specific wall components. In Gram-positive bacteria the peptidoglycan is exposed and lysins can act directly; in Gram-negative bacteria outer membrane barriers often require permeabilizers or engineering to allow access.

Applications: Because of their specificity and rapid action, lysins are investigated as alternative antimicrobials, biocontrol agents in food preservation, or tools in research. Several lysins have advanced to clinical trials for systemic or topical infections, notably candidates targeting Staphylococcus aureus and Streptococcus species. Challenges include potential immunogenicity, delivery to infection sites, and the emergence of resistance, though the latter appears limited due to essential wall targets.

Notable examples: Exebacase (CF-301) is a lysin developed for Staphylococcus aureus infections; PlyC is a well-studied lysin effective against several streptococci. Research continues into improving spectrum, stability, and delivery methods.