lysins

Lysins are a class of enzymes produced by bacteriophages (and sometimes by bacteria) that degrade peptidoglycan in bacterial cell walls. They are most commonly referred to as endolysins when produced during the phage replication cycle to lyse the host cell and release progeny.

Most lysins are modular, consisting of an enzymatically active domain (EAD) and a cell-wall binding domain (CBD). The EADs include muramidases (glycosidases that hydrolyze glycosidic bonds in peptidoglycan), amidases, and various endopeptidases that cleave peptide cross-links. The CBD provides specificity by recognizing particular cell-wall components.

In a lytic infection, holins accumulate in the host cytoplasmic membrane and form lesions, allowing endolysins to access the wall; subsequent hydrolysis weakens the cell wall and triggers osmotic lysis, releasing phage particles. Lysins can also act exogenously when applied as purified enzymes under appropriate conditions, particularly against Gram-positive bacteria with exposed peptidoglycan.

Applications include phage therapy and development of enzybiotics for treating antibiotic-resistant infections, biocontrol in foods and agriculture, and industrial decontamination. Engineered lysins, including chimeric lysins with altered EADs or CBDs and Artilysins that combine lysins with outer-membrane permeabilizers, aim to broaden host range and improve activity against Gram-negative pathogens.

Limitations and considerations include delivery and stability in vivo, potential immunogenic responses, production costs, and regulatory status. Resistance to lysins is considered less common than with traditional antibiotics, but emerging mechanisms and combination therapies are under study.