Antibacterial properties of a pre-formulated recombinant phage endolysin, SAL-1

To evaluate the phage endolysin SAL-1 as a therapeutic agent for Staphylococcus aureus infections, the in vitro and in vivo antibacterial properties of a pre-formulation containing recombinant SAL-1 as an active pharmaceutical ingredient were investigated. The stable pre-formulation (designated SAL2...

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Bibliographic Details
Published in:International journal of antimicrobial agents 2013-02, Vol.41 (2), p.156-161
Main Authors: Jun, Soo Youn, Jung, Gi Mo, Yoon, Seong Jun, Oh, Myoung-Don, Choi, Yun-Jaie, Lee, Woo Jong, Kong, Joon-Chan, Seol, Jae Goo, Kang, Sang Hyeon
Format: Article
Language:English
Subjects:
amino acids
animal models
Animals
Anti-Bacterial Agents - isolation & purification
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
anti-infective agents
Anti-Staphylococcus aureus agent
antibacterial properties
Bactericidal
bacteriophages
blood flow
blood serum
calcium
Chemistry, Pharmaceutical
Chromatography, Liquid
culture media
Disease Models, Animal
drug formulations
encapsulation
endolysin
Endopeptidases - genetics
Endopeptidases - isolation & purification
Endopeptidases - pharmacology
Endopeptidases - therapeutic use
Female
Humans
hydrophobic interaction chromatography
Infectious Disease
ingredients
Injections, Intravenous
intravenous injection
ion exchange
ions
Mice
Mice, Inbred ICR
Microbial Sensitivity Tests
Microbial Viability - drug effects
minimum inhibitory concentration
patients
Phage endolysin
plate count
Recombinant Proteins - genetics
Recombinant Proteins - isolation & purification
Recombinant Proteins - pharmacology
Recombinant Proteins - therapeutic use
SAL-1
Staphylococcal Infections - drug therapy
Staphylococcal Infections - microbiology
Staphylococcus aureus
Staphylococcus aureus - drug effects
Staphylococcus aureus - isolation & purification
Survival Analysis
temperature
Treatment Outcome
viability
Viral Proteins - genetics
Viral Proteins - isolation & purification
Viral Proteins - pharmacology
Viral Proteins - therapeutic use
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Summary:To evaluate the phage endolysin SAL-1 as a therapeutic agent for Staphylococcus aureus infections, the in vitro and in vivo antibacterial properties of a pre-formulation containing recombinant SAL-1 as an active pharmaceutical ingredient were investigated. The stable pre-formulation (designated SAL200) uniquely included calcium ions and Poloxamer 188 as enhancing and stabilising ingredients, respectively. SAL-1 was successfully produced with no extraneous amino acids by decreasing the culture temperature and was highly purified using a two-step chromatography procedure consisting of ion exchange and hydrophobic interaction chromatography. SAL200 exhibited rapid and effective bactericidal activity against encapsulated and biofilm-forming S. aureus as well as against planktonic S. aureus cells. In addition, SAL200 demonstrated increased effectiveness in the serum environment, with a significantly reduced minimum bactericidal concentration compared with that determined in culture medium. In in vitro antibacterial tests performed against 425 clinical isolates [including 336 meticillin-resistant S. aureus (MRSA) isolates and 1 vancomycin-intermediate S. aureus isolate], collected from 421 patients and four animals, SAL200 exhibited obvious antibacterial activity against all S. aureus isolates tested. Intravenous injection of SAL200 in a mouse model of MRSA infection prolonged the viability of mice and significantly reduced bacterial counts in the bloodstream and splenic tissue. The results presented in this article strongly support SAL200 as a highly potent bactericidal agent against MRSA with an adequate pharmaceutical formulation.
ISSN:0924-8579
1872-7913
DOI:10.1016/j.ijantimicag.2012.10.011