A stable phage lysin (Cpl-1) dimer with increased antipneumococcal activity and decreased plasma clearance.

Details

Serval ID
serval:BIB_093242ED7AD8
Type
Article: article from journal or magazin.
Collection
Publications
Title
A stable phage lysin (Cpl-1) dimer with increased antipneumococcal activity and decreased plasma clearance.
Journal
International Journal of Antimicrobial Agents
Author(s)
Resch G., Moreillon P., Fischetti V.A.
ISSN
1872-7913 (Electronic)
ISSN-L
0924-8579
Publication state
Published
Issued date
2011
Volume
38
Number
6
Pages
516-521
Language
english
Abstract
Bacteriophages (phages) produce endolysins (lysins) as part of their lytic cycle in order to degrade the peptidoglycan layer of the infected bacteria for subsequent release of phage progeny. Because these enzymes maintain their lytic and lethal activity against Gram-positive bacteria when added extrinsically to the cells, they have been actively exploited as novel anti-infectives, sometimes termed enzybiotics. As with other relatively small peptides, one issue in their clinical development is their rapid inactivation through proteolytic degradation, immunological blockage and renal clearance. The antipneumococcal lysin Cpl-1 was shown to escape both proteolysis and immunological blockage. However, its short plasma half-life (20.5 min in mice) may represent a shortcoming for clinical usefulness. Here we report the construction of a Cpl-1 dimer with a view to increasing both the antipneumococcal specific activity and plasma half-life of Cpl-1. Dimerisation was achieved by introducing specific cysteine residues at the C-terminal end of the enzyme, thus favouring disulphide bonding. Compared with the native monomer, the constructed dimer demonstrated a two-fold increase in specific antipneumococcal activity and a ca. ten-fold decrease in plasma clearance. As several lysins are suspected to dimerise on contact with their cell wall substrate to be fully active, stable pre-dimerised enzymes may represent a more efficient alternative to the native monomer.
Pubmed
Web of science
Create date
12/12/2011 16:13
Last modification date
20/08/2019 13:31
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