The United States of America; as Represented by the Secretary of Agriculture
发明人:
David M. Donovan
申请号：
US14503397
公开号：
US20160097044A1
申请日:
2014.10.01
申请国别(地区):
US
年份:
2016
代理人:
摘要：
Multi-drug resistant bacteria are a persistent problem in modern health care, food safety and animal health. There is a need for new antimicrobials to replace over-used conventional antibiotics. Here we describe engineered triple-acting staphylolytic peptidoglycan hydrolases wherein three unique antimicrobial activities from two parental proteins are combined into a single fusion protein, effectively reducing the incidence of resistant strain development. The fusion protein reduced colonization by S. aureus in a rat nasal colonization model, surpassing the efficacy of either parental protein. Modification of the triple-acting lytic construct with a protein transduction domain significantly enhanced both biofilm eradication and the ability to kill intracellular Staphylococcus aureus as demonstrated in cultured cells, and mouse models of staphylococcal mastitis and osteomyelitis. Bacterial cell wall degrading enzyme antimicrobials can be engineered to enhance their value as potent therapeutics.
