Lysin

Lysins, also known as endolysins or murein hydrolases, are hydrolytic enzymes produced by bacteriophages in order to cleave the host's cell wall during the final stage of the lytic cycle. Lysins are highly evolved enzymes that are able to target one of the five bonds in peptidoglycan (murein), the main component of bacterial cell walls, which allows the release of progeny virions from the lysed cell. Cell-wall-containing Archaea are also lysed by specialized pseudomurein-cleaving lysins, while most archaeal viruses employ alternate mechanisms. Similarly, not all bacteriophages synthesize lysins: some small single-stranded DNA and RNA phages produce membrane proteins that activate the host's autolytic mechanisms such as autolysins. Lysins, also known as endolysins or murein hydrolases, are hydrolytic enzymes produced by bacteriophages in order to cleave the host's cell wall during the final stage of the lytic cycle. Lysins are highly evolved enzymes that are able to target one of the five bonds in peptidoglycan (murein), the main component of bacterial cell walls, which allows the release of progeny virions from the lysed cell. Cell-wall-containing Archaea are also lysed by specialized pseudomurein-cleaving lysins, while most archaeal viruses employ alternate mechanisms. Similarly, not all bacteriophages synthesize lysins: some small single-stranded DNA and RNA phages produce membrane proteins that activate the host's autolytic mechanisms such as autolysins. Lysins are being used as antibacterial agents due to their high effectiveness and specificity in comparison with antibiotics, which are susceptible to bacterial resistance. The first lysin (Exebacase) developed at the Rockefeller University and licensed by ContraFect Corp, has successfully completed phase 2 human clinical trials to treat methicillin resistant Staphylococcus aureus (MRSA) bacteremia (contrafect.com). Double-stranded DNA phage lysins tend to lie within the 25 to 40 kDa range in terms of size. A notable exception is the streptococcal PlyC endolysin, which is 114 kDa. PlyC is not only the biggest and most potent lysin, but also structurally unique since it is composed of two different gene products, PlyCA and PlyCB, with a ratio of eight PlyCB subunits for each PlyCA in its active conformation. All other lysins are monomeric and comprise two domains separated by a short linker region. For gram positive bacteria lysins, the N-terminal domain catalyses the hydrolysis of peptidoglycan whereas the C-terminal domain binds to the cell wall substrate.