OBJECTIVES: Phage-coded lysins, i.e. murein hydrolases, are enzymes that destroy the cell wall of bacteria. A rapid killing of @entity328 in the nasopharynx of @entity19 has been described recently using a phage-coded murein hydrolase (enzybiotic). The in vivo effects of a dose-ranging treatment, using either of the phage-coded lytic enzymes @entity69562 lysozyme or the @entity15409 amidase, have been investigated here in a @entity19 @entity295 model. METHODS: Purified @entity15409 amidase and/or @entity69562 lysozyme were used alone or in combination. These enzymes were injected intraperitoneally at different times after challenge with 5 x 10(7) cfu of a type 6B, antibiotic-resistant @entity2260 clinical isolate. RESULTS: Animals challenged with 5 x 10(7) cfu of this strain alone died within 72 h, whereas a single intraperitoneal injection of @entity69562 or @entity15409 (200 microg; 1100 U) administered 1 h after the bacterial challenge was sufficient to effectively protect the @entity19 , according to unpaired t-test (P<0.0001). @entity582 in unprotected @entity19 reached colony counts >10(7) cfu/mL, whereas the mean colony count in lysin-protected animals was <10(6) cfu/mL over time and ultimately became undetectable. Interestingly, a synergic effect in vivo was observed with the combined use of 2.5 microg each of @entity69562 and @entity15409 . CONCLUSIONS: Our findings suggest strongly that phage lysins protect animals from @entity582 and @entity204 . Moreover, the simultaneous attack of the pneumococcal peptidoglycan by a lysozyme and an amidase leads to a remarkable effect through enhanced destruction of the bacterial cell wall. The benefits of therapy with enzybiotics against pneumococcus reported here might warrant the examination of alternative strategies for the treatment of diseases caused by clinically relevant pathogens.

Phage lytic enzymes as therapy for antibiotic-resistant @entity328 infection in a @entity19 XXXX model.

@entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity69562 :: ('107463(Tax:10090)', 'Gene') :: ['Cpl-1'] @entity19 :: ('10090', 'Species') :: ['mice', 'murine'] @entity2260 :: ('2104', 'Species') :: ['S. pneumoniae'] @entity582 :: ('MESH:C531821', 'Disease') :: ['bacteraemia', 'Bacteraemia'] @entity15409 :: ('CHEBI:59043', 'Chemical') :: ['Pal'] @entity328 :: ('1313', 'Species') :: ['Streptococcus pneumoniae'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death']
@entity295 :: (MESH:D018805,Disease) :: ['sepsis']
