Bacteriophage Lysins

BACTERIOPHAGE LYSINS  

Bacteriophage lysins were described as which phages are released from the host cells they have infected. They are generally a two-component enzyme system consisting of holins which attack the cytoplasmic membrane and endolysins which then degrade the cell wall peptidoglycan. The latter are heat-stable enzymes capable of being isolated and purified, sometimes using recombinant techniques. When small quantities of these purified lysins are applied to cultures of bacteria they achieve extremely rapid lysis and have been reported to give greater than 6-log reduction in a matter of seconds. Characteristics such as this have led to the generation of great interest in these agents as possible alternatives to antibiotics.

The bacteriophage lysins are similar in some ways to enzymes such as lysozyme in that they are able to degrade intact peptidoglycan. This weakens the cell wall and the internal hydrostatic pressure causes the wall to rupture. Access to the peptidoglycan layer is critical, however, and although this is readily achieved in Gram-positive bacteria, the presence of an outer membrane in Gram-negative bacteria makes them resistant to the effects of these enzymes. An interesting feature of the endolysins is that they are specific for the bacteria from which they were generated, thus giving them the same specificity as the bacteriophages. This has some advantages in that the normal microflora of the body will not be affected; they do not, however, have the self-replication characteristics of phages and so behave like an ordinary drug.

Most antibiotics are small molecules which are not usually immunogenic, but the endolysins are proteins with molecular weights in the region of 25–40 kDa which makes them potentially capable of stimulating an immune response. Animal experimentation has shown that when administered systemically the endolysins have a very short half-life because they are neutralized by the immune system. However, they are still able to produce a satisfactory antimicrobial effect because their action is so rapid.

An interesting idea which has been put forward is to use the endolysins for prophylaxis as a means of reducing the bioburden of mucous membranes. in particular eliminating potential pathogens such as Staph. aureus and Strep. pneumoniae. Both of these organisms are responsible for secondary bacterial respiratory tract infections following an initial viral infection. It is proposed that removal of these bacteria from the mucous membranes would significantly reduce the chances of secondary infection. The hypothesis has been supported by animal models but requires clinical trials for verification.