Antimicrobial Agent
ALL
Pal (alone)
+ Cpl-1
Study Type
ALL
in vitro
in vivo
Model
ALL
Bacteria
Mouse
Administration
ALL
n/a
intranasal
intraperitoneal
Relevant Results Adverse Effects and Other Issues Reference ?
Pal
in vitro
15 clinical Streptococcus pneumoniae strains obtained from various sources (each of which represented distinct serotype); including 3 highly penicillin-resistant strains
Efficient lytic activity against all 15 clinical strains tested.
Within 30 sec, 100 U/mL of Pal decreased the viable titer in encapsulated and highly penicillin-resistant strains by a median of 4.00 log10 CFU /mL. Moreover, penicillin intermediate and highly penicillin resistant strains were lysed at essentially the same rates as penicillin sensitive strains.
11739958
Pal
in vivo
murine model of nasopharyngeal colonization
intranasal
Single topical dose of Pal administered to mice 42 h after inoculation with pneumococci was sufficient to completely eliminate the bacterial colonization from the surface of the mucous membrane 5 h after treatment.
11739958
Pal + Cpl-1
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 Pal at the final concentration of 1U/mL significantly reduced bacterial titers of the 4 strains by 1.34 log10 CFU /mL and in 10 min 1.99 log10 CFU /mL.
Killing efficacy was always significantly higher for combination of lysins than that of single agent alone, reducing titers by a median of 2.40 (30 sec) and 3.15 (10 min) log10 CFU /mL respectively, demonstrated synergism.
12499217
Pal + Cpl-1
in vivo
murine peritonitis-sepsis model
intraperitoneal
Single dose of Pal (200 µg) administered 1 h after inoculation rescued 100% of the mice (same as Cpl-1) 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