Triple-acting Lytic Enzyme Treatment of Drug-Resistant and Intracellular Staphylococcus aureus
Year: 2016
Type: article
Abstract: 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. This effectively reduces the incidence of resistant strain development. The fusion protein reduced colonization by Staphylococcus aureus in a rat nasal colonization model, surpassing the efficacy of either parental protein. Modification of a triple-acting lytic construct with a protein transduction domain significantly enhanced both biofilm eradication and the ability to kill intracellular S. aureus as demonstrated in cultured mammary epithelial cells and in a mouse model of staphylococcal mastitis. Interestingly, the protein transduction domain was not necessary for reducing the intracellular pathogens in cultured osteoblasts or in two mouse models of osteomyelitis, highlighting the vagaries of exactly how protein transduction domains facilitate protein uptake. Bacterial cell wall degrading enzyme antimicrobials can be engineered to enhance their value as potent therapeutics.
Source: Scientific Reports
DOI: 10.1038/srep25063
Authors: Stephen C. Becker, Dwayne R. Roach, Vinita S. Chauhan, Yang Shen, Juli Foster-Frey, Anne M. Powell, Gary Bauchan, Richard A. Lease, Homan Mohammadi, William J. Harty, Chad Simmons, Mathias Schmelcher, Mary Camp, Shengli Dong, John R. Baker, Tamsin R. Sheen, Kelly S. Doran, David G. Pritchard, Raul A. Almeida, Daniel C. Nelson, Ian Marriott, Jean C. Lee, David M. Donovan
Institutions: Agricultural Research Service, University of North Carolina at Charlotte, Institute for Bioscience and Biotechnology Research, University of Maryland, College Park, University of Alabama at Birmingham, San Diego State University, University of Tennessee at Knoxville, Brigham and Women's Hospital, Harvard University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W2345020184