Developing Bacterial Virus Deterrents to Challenges of Impending Postantibiotic Era: Phage Product Engineering, Therapy, Vaccines

Dear Colleagues,

The possibility for identifying substances produced by bacteria that inhibited the growth of other bacteria was realized only a few years before the term antibiotic was coined by Waksman in 1943 (following the discoveries of penicillin and streptomycin). This represented a significant change in the philosophical approach to combating infectious disease. The term was used to designate substances of microbial origin which specifically inhibited the growth (biosynthetic activity) or integrity of other microbes. The further discovery and exploitation of these wonder drugs enabled elective surgeries and proved a deterrent to widespread ravages of infectious microorganisms plaguing the pre-antibiotic era. In the ensuing 80 years it has become increasingly more evident that bacteria can acquire mutations or genetic elements that confer resistance, or multiple levels of resistance, to antibiotics. A future post-antibiotic era threatens. In the two decades prior to the birth of antibiotics, Felix d’Herelle recognized the existence of natural substances, he termed phages, that could infect, multiply within, and burst from bacterial cells. Phage therapy was advanced as a means by which predator bacterial viruses could be exploited to contain infectious bacteria. We have come to realize that while phages represent the predominant microorganisms within the biosphere, the process and outcome of a phage infection is highly unique to the phage and target cell. Modern genetics, protein engineering, and data mining, can supplement the selection for compatible matches derived from natural sources. The thesis advanced is that with the wealth of modern molecular technology, bacterial viruses can finally be rationally exploited as antibiotic substitutes or as co-therapies to treat infectious disease. This can include strategies to identify and characterize receptors involved in phage-host interactions, the engineering of phages or their encoded proteins to target and kill selected bacterial cells, and the use of phages to display or express peptides that serve as vaccines or therapeutic agents.

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• phage product engineering
• phage therapy
• phage vaccines