Lysin

Endolysins (also murein hydrolases ) are hydrolytic enzymes (abbreviated phage ) of bacteriophage encoded and are produced by bacteria during infection. They are produced in the final phase of the lytic cycle, to cut the cell wall of the host bacteria at specific sites and to ensure that the release of the phage progeny. Endolysins are highly specialized enzymes that dissolve the cell walls of Gram-positive bacteria and therefore act as bacteriocins. Endolysins hydrolyze the murein in the peptidoglycan of bacterial cell walls, so they are discussed inter alia as an alternative for the treatment of antibiotic-resistant bacteria. So far there is only one approved as a medical device enzyme ( in creams and gels the endolysin Staphefekt is used ), but no corresponding Arnzeimittelzulassungen.

Properties

Lytic bacteriophages have to be specific bacterial viruses with their hosts developed in the course of evolution and have adapted over again. This also endolysins have been optimized in their effect over millions of years and have - as their phage - a corresponding host specificity. Can they develop because they do not recognize the surface structures of the bacteria and not find the right connections in the bacterial envelope does not have effect, they do not exert any effect.

Phagenendolysine against Gram-positive bacteria have a modular structure, wherein the catalytically active protein domains are spaced apart from the areas that are responsible for the detection of bacterial surface molecules. For the recognition and binding to a cell wall, the cell wall binding domain provides ( engl. cell wall binding domain, CBD). The enzyme- cally active domains ( EAD) can amidases, endopeptidases, glucosaminidases, muramidases be, inter alia, the different classes of enzymes cleave only very specific, typical for their respective host connections within the bacterial Peptidoglykanhülle. The endolysins each cleave one for each bacterial species specific, highly conserved compound in the Peptidoglykanhülle, so that it is irreparably damaged. The holey bacterial envelope can the high internal osmotic pressure can not withstand, and the bacterium bursts, causing the newly formed bacteriophages are released. This lytic effect of outside ( ' exolytisch ') can endolysins in Gram-negative bacteria do not develop directly, as these an outer membrane hinders access to Peptidoglykanhülle.

Effectiveness

Due to the co-evolution of bacteria and bacteriophage phage lysines are usually species-specific or even strain - specific. They can therefore act only against those bacterial species or strains of bacteria, for which the respective phage from which they have been isolated, was specific. A development of resistance to phage endolysins the part of the bacteria is considered to be extremely improbable event and so far has not been demonstrated in laboratory experiments. Unlike antibiotics, which penetrate into the bacteria and engage in different ways in the metabolism, act directly from the outside administered endolysins so that bacteria get less chance to adapt.

Side effects

Unlike antibiotics, they appear neither to other bacterial species, nor to plant, animal or human cells due to the limited spectrum of action. An allergic reaction in sensitive individuals can not be ruled out completely, since endolysins are proteins.

Applications

Endolysins be examined among other things for use against Gram- positive bacteria on mucous membranes, resulting in systemic infection, in diagnostics, for defense against bioterrorism, for eliminating food pathogens and the reduction of plant damage in agriculture.

In creams and gels for the brand Gladskin the Dutch company Micreos Human Health endolysin Staphefekt is used. These medical devices are to alleviate symptoms of acne, rosacea, eczema, razor bumps and other skin irritations. The enzyme was developed in collaboration with the Swiss Federal Institute of Technology ( ETH) Zurich. Staphefekt is an endolysin, which originally comes from a Staphylococcus aureus - infecting phages. It exerts its antibacterial effect almost exclusively to bacteria of the species Staphylococcus aureus ( S. aureus), which are often involved in infections, including the inflammatory symptoms of various skin disorders. The endolysin Staphefekt SA.100 has three functional sections, each with different functions and jointly convey a narrow host specificity: a CBD for the recognition and binding to the surface molecules of S. aureus and two enzymatically active domains, an endopeptidase and an amidase.