中文摘要：金黄色葡萄球菌是医院和社区获得性感染最常见的原因。目前临床治疗受到耐药菌株出现的限制。之前开发的嵌合ClyC，可有效抑制金黄色葡萄球菌，但还需要一个有效的输送系统，向感染部位持续释放ClyC。为此，本研究设计了一种负载ClyC的海藻酸盐水凝胶（ClyC-AH），以改善对金黄色葡萄球菌的治疗效果。ClyC-AH保留了ClyC的稳定性和活性，同时提供了ClyC的缓释和对金黄色葡萄球菌的持续抗菌作用。与单独使用ClyC相比，使用ClyC-AH相对安全，在ClyC浓度<=250μg/ml时，对BHK-21细胞没有明显的细胞毒性。此外，在金黄色葡萄球菌感染的小鼠骨髓炎模型中，ClyC-AH降低了股骨和周围组织的细菌负荷，活菌数量减少了2 log（10）（CFU/ml）。可见，水凝胶递送的嵌合细胞裂解酶ClyC在金黄色葡萄球菌靶向治疗中具有广阔的前景。
外文摘要：Staphylococcus aureus (S. aureus) is the most common cause of hospital and community-acquired infections. The current clinical treatment is limited by the emergence of drug-resistant strains. We previously developed a chimeric ClyC that effectively inhibited S. aureus strains. Nonetheless, an efficient delivery system to provide sustained release of ClyC to infected site is needed. Thus, we engineered a chimeric ClyC loaded alginate hydrogel (ClyC-AH) to improve the therapeutic outcomes against S. aureus. ClyC-AH retained the stability and activity of ClyC while providing a sustained release of ClyC and a continuous antibacterial effect against S. aureus. Compared to ClyC alone, the use of ClyC-AH was relatively safe, as there was no significant cytotoxicity to BHK-21 cells at a ClyC concentration <= 250 mu g/ml. Furthermore, in a S. aureus infected mouse model of osteomyelitis, ClyC-AH reduced bacterial burden in the femur and surrounding tissues, with a reduction of 2 log(10) (CFU/ml) in viable bacterial number. Based on these results, hydrogel-delivered chimeric lysin ClyC provides a promising future in the S.aureus targeting therapy.
外文关键词：Staphylococcus aureus；MRSA；osteomyelitis；anti-bacterial activity；bacteriophage lysin；alginate hydrogel
作者：Yao, FF；Wu, XY；Liao, YL；Yan, Q；Li, YH
作者单位：Wuhan Univ
期刊名称：FRONTIERS IN MATERIALS
期刊影响因子：2.705
出版年份：2021
出版刊次：
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