Name

Cpl-1

Recommended Name ?lysozyme
Systematic Name ?peptidoglycan N-acetylmuramoylhydrolase
Alternative Name ?CP-1 lysin
1,4-N-acetylmuramidase
mucopeptide glucohydrolase
mucopeptide N-acetylmuramoylhydrolase
muramidase
N,O-diacetylmuramidase
peptidoglycan N-acetylmuramoylhydrolase
Uniprot IDP15057
General Mode of ActionEnzymatic cleavage of peptidoglycan which results in a rapid lysis of the bacterial cell.
phiBIOTICS Family ?Lysozyme
Reaction ?1. Catalysis of the hydrolysis of the beta-(1->4) linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins
    EC: 3.2.1.17
    Corresponding Pfam domain: Glyco_hydro_25
    Evidence: experimental (PubMed: 1390634)
Source Organism ?Streptococcus phage Cp-1
Target Organism ?Streptococcus pneumoniae
Disease ?Meningitis
Otitis media
Pneumonia
Septicemia
State ?Tested
Reference ?1390634
3422470
14527392
14573637


Studies found: 10

Antimicrobial Agent
Study Type
Model
Administration
Relevant ResultsAdverse Effects and Other IssuesReference ?
Cpl-1 in vivo
  • mouse model of pneumococcal bacteremia
 intravenous

 Single dose of Cpl-1 (2000 µg) administered 1 h after intravenous infection resulted in rapid (within 15 min) decrease of bacterial titers to undetectable levels and led to 100% survival at 48 h compared to the 20% survival of untreated controls. Toxicity
Repeated administration of large amounts of Cpl-1 revealed no signs of toxicity in the treated animals for 4 weeks.

Other Issues
Rapid decrease of enzyme activity occured after treatment with NaCl, a concentration of or above 300 mM (two times the physiological concentration).
The pH optimum for enzyme was found between 4 and 5 and complete loss of activity was observed at ph values above 8 and below 3.		 14573637
Cpl-1 in vivo
  • rat model of experimental endocarditis
 intravenous

 Administration of Cpl-1 (250 mg/kg) followed by continuous infusion (250 mg/kg/h) for 6 h cleared pneumococci from blood within 30 min and almost complete elimination of bacteria was maintained over the next 6 h. Toxicity
Untreated pneumococcal endocarditis induced the release of IL-1α, IL-1β, IL-6, IL-10, IFN-γ, TNF but not IL-2, IL-4, or GM-CSF.
High concentration of Cpl-1 resulted in fragmentation of the bacterial cell wall and induce accentuated cytokine secretion noticeably, but no deterioration of lysin activity was observed.		 16251333
Cpl-1 in vivo
  • murine model for acute otitis media
 intranasal

 Administration of two topical doses of Cpl-1 resulted in complete prevention of otitis media by entire elimination of bacterial colonization in 90% of the mice. 17381239
Cpl-1 in vivo
  • murine β-lactam-resistant peritonitis-sepsis model
 intraperitoneal

intravenous

 Single dose of Cpl-1 administered 1 h after inoculation with pneumococci resulted in 4 to 5 logs decrease of bacterial titers in blood and intraperitoneal fluid.
Antibacterial effect was observed after administration either low-dose (1.4 mg; 47 mg/kg) or high-dose (3.3 mg; 110 mg/kg) of enzyme.		 17827138
Cpl-1 in vivo
  • murine model of nasopharyngeal colonization
 intranasal

 Single dose of Cpl-1 (1000 µg) resulted in elimination of bacterial colonization in mice.
Enzyme potent killing activity was found to be as efficient as other pneumococcal phage enzyme described previously Pal amidase.		 14573637
Cpl-1 in vivo
  • infant-rat model of experimental pneumococcal meningitis
 intracisternal

intraperitoneal

 Single intracisternal injection of Cpl-1 (~20 mg/kg) resulted in a rapid (within 30 min) reduction of pneumococci in the CSF by 3 orders of magnitude lasting for 2 h. After intraperitoneal injection of Cpl-1 (~200 mg/kg) pneumococal titers in CSF dropped by 2 orders of magnitude for 3 h. Other Issues
Half-life of Cpl-1 in CSF was estimated to be ~16 min and therefore temporally defined antibacterial effect of enzyme. Following intracisternal administration antibacterial effect was detectable in CSF for as long as 3 h after initiation of the treatment; intraperitoneal administration extend this effect up to 4 h after injection due to prolonged systemic release of the enzyme.		 18471063
Cpl-1 + Gentamicin in vitro
  • Streptococcus pneumoniae strains with various susceptibilities to penicillin:
    DCC1490
    DCC1476
    DCC1420
    8249
 Combination of Cpl-1 with GEN resulted in effective synergistic inhibition (with a 1.000 fold-lower final titer in combination than with the most active agent alone) against more susceptible S. pneumoniae strains DCC1490 and DCC147; thus showed increasing synergy with a decresing penicillin MIC. 15728935
Cpl-1 + Penicillin in vitro
  • Streptococcus pneumoniae strains with various susceptibilities to penicillin:
    DCC1490
    DCC1476
    DCC1420
    8249
 Combination of Cpl-1 with PEN resulted in effective synergistic inhibition (with a 10.000-fold lower final titer than with the most active agent alone) against an extremely PRSP strains DCC1420 and 8249. 15728935
Cpl-1 + Pal in vitro
  • Streptococcus pneumoniae strains including highly penicilin resistant strains:
    DCC1355
    DCC1490
    DCC1494
    DCC1335
    DCC1420
    (each representing distinct serotype)
 Efficient lytic activity against all strains tested.
In 30 sec 150 µL of Cpl-1 at the final concentration of 1 U/mL significantly reduced bacterial titers of the four strains by 0.83 log10 CFU/mL and in 10 min 1.44 log10 CFU/mL.
Killing efficacy of the combination of Cpl-1 and Pal was always significantly higher than that of single enzyme, reducing titers by a median of 2.40 (30 sec) and 3.15 (10 min) log10 CFU/mL respectively, demonstrated synergism.		 12499217
Cpl-1 + Pal in vivo
  • murine peritonitis-sepsis model
 intraperitoneal

 Single dose of Cpl-1 (200 µg) administered 1 h after inoculation rescued 100% of the mice (same as Pal amidase) with very rapid antibacterial activity (decrease of bacterial titers ~4 log units 2 h after treatment).
Combined treatment with both enzymes resulted in synergistic effect and was found with different doses and administration times.		 Toxicity
Titres of specific IgG antibodies measured 10 days after injection of enzyme were 8 times higher in hyperimunne than preimunne serum.

Health Effect
No signs of anaphylaxis or adverse side effects were observed.

Other Issues
Effective protection was achieved only with functional enzymes, with heat-inactivated enzymes rescue did not occur.		 14613958