Engineered Phagemids for Nonlytic, Targeted Antibacterial Therapies
Author(s)Krom, Russell-John; Saluja, Prerna; Lobritz, Michael Andrew; Collins, James J.
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The increasing incidence of antibiotic-resistant bacterial infections is creating a global public health threat. Because conventional antibiotic drug discovery has failed to keep pace with the rise of resistance, a growing need exists to develop novel antibacterial methodologies. Replication-competent bacteriophages have been utilized in a limited fashion to treat bacterial infections. However, this approach can result in the release of harmful endotoxins, leading to untoward side effects. Here, we engineer bacterial phagemids to express antimicrobial peptides (AMPs) and protein toxins that disrupt intracellular processes, leading to rapid, nonlytic bacterial death. We show that this approach is highly modular, enabling one to readily alter the number and type of AMPs and toxins encoded by the phagemids. Furthermore, we demonstrate the effectiveness of engineered phagemids in an in vivo murine peritonitis infection model. This work shows that targeted, engineered phagemid therapy can serve as a viable, nonantibiotic means to treat bacterial infections, while avoiding the health issues inherent to lytic and replicative bacteriophage use.
DepartmentInstitute for Medical Engineering and Science; MIT Synthetic Biology Center; Broad Institute of MIT and Harvard; Massachusetts Institute of Technology. Department of Biological Engineering
American Chemical Society (ACS)
Krom, Russell J.; Bhargava, Prerna; Lobritz, Michael A. and Collins, James J. “Engineered Phagemids for Nonlytic, Targeted Antibacterial Therapies.” Nano Letters 15, no. 7 (July 2015): 4808–4813. © 2015 American Chemical Society
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