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. 2018 Jun 7;10(6):310.
doi: 10.3390/v10060310.

Development of Phage Lysins as Novel Therapeutics: A Historical Perspective

Vincent A Fischetti  1
Affiliations

Development of Phage Lysins as Novel Therapeutics: A Historical Perspective

Vincent A Fischetti. Viruses. .

Abstract

Bacteriophage lysins and related bacteriolytic enzymes are now considered among the top antibiotic alternatives for solving the mounting resistance problem. Over the past 17 years, lysins have been widely developed against Gram-positive and recently Gram-negative pathogens, and successfully tested in a variety of animal models to demonstrate their efficacy. A lysin (CF-301) directed to methicillin resistant Staphylococcus aureus (MRSA) has effectively completed phase 1 human clinical trials, showing safety in this novel therapeutic class. To validate efficacy, CF-301 is currently the first lysin to enter phase 2 human trials to treat hospitalized patients with MRSA bacteremia or endocarditis. If successful, it could be the defining moment leading to the acceptance of lysins as an alternative to small molecule antibiotics. This article is a detailed account of events leading to the first therapeutic use and ultimate development of phage-encoded lysins as novel anti-infectives.

Keywords: alternative to antibiotics; antibiotic resistance; discovery; endolysins; lysins; lytic enzymes; phage; therapeutic.

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Conflict of interest statement

The author is a consultant for ContraFect Corporation and is an equity holder in the company. He also receives grant support from ContraFect.

Figures

Figure 1
Figure 1
The cover of Nature, 22 August 2002, showing the cover article of a phage lysin against Bacillus anthrax. The cover image is a bacillus after treatment with the PlyG lysin, showing the cytoplasmic membrane externalizing (white circle and at the top of the bacillus).
See this image and copyright information in PMC

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