title: Antibacterial properties of a pre-formulated recombinant phage endolysin, SAL-1.
abstract: 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.
authors.affiliation: iNtRON Biotechnology, Inc., Room 903, JungAng Induspia V, 138-6, Sangdaewon-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-120, Republic of Korea.
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Jun
authors.forename: Gi Mo
authors.initials: GM
authors.lastname: Jung
authors.forename: Seong Jun
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Myoung-Don
authors.initials: MD
authors.lastname: Oh
authors.forename: Yun-Jaie
authors.initials: YJ
authors.lastname: Choi
authors.forename: Woo Jong
authors.initials: WJ
authors.lastname: Lee
authors.forename: Joon-Chan
authors.initials: JC
authors.lastname: Kong
authors.forename: Jae Goo
authors.initials: JG
authors.lastname: Seol
authors.forename: Sang Hyeon
authors.initials: SH
authors.lastname: Kang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D016019:Survival Analysis; D016896:Treatment Outcome; D014764:Viral Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D011994:Recombinant Proteins; D014764:Viral Proteins; D010450:Endopeptidases; C001143:endolysin