Autolysin

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Background

Autolysin is the main peptidoglycan hydrolase in Staphylococcus. It is a bifunctional protein consisting of a propeptide region, an amidase, and an endo-β-N-acetylglucosaminase domain. Autolysin is processed to produce two extracellular lysozymes that attach noncovalently to the surface of Staphylococcal cells. Bacterial autolysin is an endogenous enzyme that breaks the covalent bonds of its cell wall peptidoglycan. These molecules are involved in various biological functions such as cell wall turnover, cell segregation, cell division, and antibiotic-induced autolysis. There is also evidence that autolysin contributes to the pathogenicity of Gram-positive bacteria. Full autolysis function is required for the full expression of Streptococcus pneumoniae virulence. Staphylococcus aureus mutants deficient in autolysis are weakly virulent in endocarditis models. Various phage-encoded autolysins that act as peptidoglycan hydrolases have been seen to contain conserved amidase motifs of bacterial amidases, eukaryotic glutathionylspermidine amidase, NLP-/P60 family proteins, and glutamyl L-diamino endopeptidases. The first autolysin to be used as an antimicrobial agent was LytA amidase from Streptococcus pneumoniae.

Fig.1 Natural context of action of phage lytic enzymes (PLEs).

Functions

Autolysin has various functions: it is involved in the separation of the daughter cells by hydrolyzing the amide bond between N-acetylmuramic acid and L-alanine; it acts directly as an adhesin by binding to fibronectin and vitronectin mainly via the peptidoglycan binding domains; it is involved in biofilm formation; and finally, autolysin mutants were attenuated in pathogenesis in an intravascular catheter-associated rat infection model. Autolysin is a sec-dependent output and it has been demonstrated that mural phosphocholine acid plays a crucial role in the targeting of phage-derived autolysin to the septal zone. Bacterial murein hydrolases, also known as autolysins, are involved in the production of biofilms. They are important contributors to cell wall growth and regulation, as well as several lysis processes. Because of its role in cell wall regulation, autolysin may affect the localization of cell wall anchoring proteins that are important for adhesion during biofilm development.

Mode of Action

Bacteria are known to utilize several different proteases involved in the assembly and disassembly of bacterial cell walls during bacterial growth and cell division. However, the synthesis and hydrolysis of peptidoglycan (PGN) are required for almost all bacterial growth processes. During bacterial cell wall conversion, several PGN hydrolases (autolysins) are produced. Autolysin is an enzyme that degrades the bond between the glycan skeleton and the stem peptide. These enzymes isolate the sugar backbone from the PGN stem peptide and are members of N-acetylmuramyl-L-alanine amidase.

The importance of bacterial proteases in bacterial viability and virulence makes them suitable targets for the development of novel antimicrobial agents. Creative Biolabs is a tight-knit team of passionate scientists, engineers, and creative thinkers, all working together towards our common goals. If you are interested in our autolysin-related services, please feel free to contact us for more.

Reference:

1. São-José, Carlos. "Engineering of phage-derived lytic enzymes: improving their potential as antimicrobials." Antibiotics 7.2 (2018): 29. Under Open Access license CC BY 4.0, without modification.