Center for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.
Department of Microbiology, Amrita Institute of Medical Sciences and Research Center, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.
J Appl Microbiol. 2021 Sep;131(3):1072-1082. doi: 10.1111/jam.14985. Epub 2021 Jan 18.
Staphylococcus aureus, an opportunistic pathogen, causes diverse community and nosocomial-acquired human infections, including folliculitis, impetigo, sepsis, septic arthritis, endocarditis, osteomyelitis, implant-associated biofilm infections and contagious mastitis in cattle. In recent days, both methicillin-sensitive and methicillin-resistant S. aureus infections have increased. Highly effective anti-staphylococcal agents are urgently required. Lysostaphin is a 27 kDa zinc metallo antimicrobial lytic enzyme that is produced by Staphylococcus simulans biovar staphylolyticus and was first discovered in the 1960s. Lysostaphin is highly active against S. aureus strains irrespective of their drug-resistant patterns with a minimum inhibitory concentration of ranges between 0·001 and 0·064 μg ml . Lysostaphin has activity against both dividing and non-dividing S. aureus cells; and can seep through the extracellular matrix to kill the biofilm embedded S. aureus. In spite of having excellent anti-staphylococcal activity, its clinical application is hindered because of its immunogenicity and reduced bio-availability. Extensive research with lysostaphin lead to the development of several engineered lysostaphin derivatives with reduced immunogenicity and increased serum half-life. Therapeutic efficacy of both native and engineered lysostaphin derivatives was studied by several research groups. This review provides an overview of the therapeutic applications of native and engineered lysostaphin derivatives developed to eradicate S. aureus infections.
金黄色葡萄球菌是一种机会致病菌，可引起各种社区和医院获得性人类感染，包括毛囊炎、脓疱疮、败血症、脓毒性关节炎、心内膜炎、骨髓炎、与植入物相关的生物膜感染和牛传染性乳腺炎。最近，耐甲氧西林和耐甲氧西林金黄色葡萄球菌感染都有所增加。迫切需要高效的抗葡萄球菌药物。溶葡萄球菌酶是一种 27 kDa 的锌金属抗菌溶细胞酶，由藤黄微球菌生物变种溶血性葡萄球菌产生，于 20 世纪 60 年代首次发现。溶葡萄球菌酶对金黄色葡萄球菌菌株具有高度活性，无论其耐药模式如何，最小抑制浓度范围在 0.001 至 0.064 μg ml 之间。溶葡萄球菌酶对分裂和非分裂的金黄色葡萄球菌细胞均有活性；并且可以渗透细胞外基质杀死嵌入生物膜的金黄色葡萄球菌。尽管具有出色的抗葡萄球菌活性，但由于其免疫原性和生物利用度降低，其临床应用受到阻碍。对溶葡萄球菌酶的广泛研究导致了几种工程化溶葡萄球菌酶衍生物的开发，这些衍生物具有降低的免疫原性和增加的血清半衰期。几个研究小组研究了天然和工程化溶葡萄球菌酶衍生物的治疗效果。本文综述了为消除金黄色葡萄球菌感染而开发的天然和工程化溶葡萄球菌酶衍生物的治疗应用。
