iNtRON Biotechnology, Inc., Room 903, JungAng Induspia V, 138-6, Sangdaewon-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-120, Republic of Korea.
Int J Antimicrob Agents. 2013 Feb;41(2):156-61. doi: 10.1016/j.ijantimicag.2012.10.011. Epub 2012 Dec 28.
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.
为了评估噬菌体溶素 SAL-1 作为金黄色葡萄球菌感染的治疗剂，研究了含有作为活性药物成分的重组 SAL-1 的预制剂的体外和体内抗菌特性。稳定的预制剂（指定为 SAL200）独特地包含钙离子和聚氧乙烯山梨醇酐脂肪酸酯 188 分别作为增强和稳定成分。通过降低培养温度成功生产了不含外源氨基酸的 SAL-1，并通过两步色谱程序（离子交换和疏水相互作用色谱）进行高度纯化。SAL200 对包封和生物膜形成的金黄色葡萄球菌以及浮游金黄色葡萄球菌细胞表现出快速有效的杀菌活性。此外，SAL200 在血清环境中表现出更高的有效性，与在培养基中确定的最小杀菌浓度相比，其最小杀菌浓度显著降低。在针对从 421 名患者和 4 只动物收集的 425 株临床分离株[包括 336 株耐甲氧西林金黄色葡萄球菌（MRSA）分离株和 1 株万古霉素中介金黄色葡萄球菌分离株]进行的体外抗菌试验中，SAL200 对所有测试的金黄色葡萄球菌分离株均表现出明显的抗菌活性。MRSA 感染小鼠模型中 SAL200 的静脉注射延长了小鼠的存活时间，并显著减少了血液和脾脏组织中的细菌计数。本文介绍的结果强烈支持 SAL200 作为一种针对 MRSA 的高效杀菌剂，具有适当的药物制剂。
