UNASSIGNED: @entity794 is a major cause of @entity281 in @entity1 and animals, causing a wide variety of diseases, from local @entity32 to fatal @entity295 . The bacterium is commonly multi-drug resistant and thus many front-line antibiotics have been rendered ineffective for treating such infections. Research on murein/peptidoglycan hydrolases, derived from bacterial viruses (bacteriophages), has demonstrated that such proteins are attractive candidates for development as novel antibacterial agents for combatting Gram positive pathogens. Here we review the research which produced to-date on the bacteriophage-derived CHAPK murein peptidase. Initially, we sequenced the genome of anti-staphylococcal @entity13794 and cloned the gene for the bacteriophage endolysin, a murein hydrolase which plays a role in cell killing during the bacteriophage life cycle. An highly active domain of the enzyme, a @entity462 , @entity3793 -dependent amido hydrolase/peptidase (CHAPK), was cloned, over-expressed in @entity526 and purified. This CHAPK enzyme was demonstrated to rapidly lyse several strains of @entity3256 resistant @entity794 and both disrupted and prevented the formation of a staphylococcal biofilm. The staphylolytic activity of the peptidase was demonstrated in vivo using a @entity19 model, without adverse effects on the animals. The crystal structure of the enzyme was elucidated, revealing a @entity460 ion close to the active site. Site-directed mutagenesis indicated that this @entity460 ion is involved in the catalytic mechanism of the enzyme. The crystal structure of this enzyme is a valuable source of information for efficient engineering of this and similar CHAP-domain-containing proteins. Overall, the data collected to date on CHAPK has demonstrated its strong potential as a novel therapeutic candidate for treatment of @entity1793 and has provided us with insight into the fundamental enzymatic mechanisms of CHAP domain-containing peptidoglycan hydrolases.

Characterization of a Bacteriophage-Derived Murein Peptidase for Elimination of Antibiotic-Resistant XXXX .

@entity1 :: ('9606', 'Species') :: ['humans'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammations'] @entity3256 :: ('MESH:D008712', 'Chemical') :: ['methicillin'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity462 :: ('MESH:D003545', 'Chemical') :: ['cysteine'] @entity3793 :: ('CHEBI:27570', 'Chemical') :: ['histidine'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity13794 :: ('221915', 'Species') :: ['bacteriophage K'] @entity794 :: ('1280', 'Species') :: ['Staphylococcus aureus', 'S. aureus'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity1793 :: ('MESH:D013203', 'Disease') :: ['staphylococcal infections'] @entity526 :: ('562', 'Species') :: ['E. coli']
@entity794 :: (1280,Species) :: ['Staphylococcus aureus']
