Title
Optimizing bacteriophage engineering through an accelerated evolution platform
Date Issued
01 December 2020
Access level
open access
Resource Type
journal article
Author(s)
Favor A.H.
Llanos C.D.
Youngblut M.D.
Nextbiotics Inc
Publisher(s)
Nature Research
Abstract
The emergence of antibiotic resistance has raised serious concerns within scientific and medical communities, and has underlined the importance of developing new antimicrobial agents to combat such infections. Bacteriophages, naturally occurring bacterial viruses, have long been characterized as promising antibiotic alternatives. Although bacteriophages hold great promise as medical tools, clinical applications have been limited by certain characteristics of phage biology, with structural fragility under the high temperatures and acidic environments of therapeutic applications significantly limiting therapeutic effectiveness. This study presents and evaluates the efficacy of a new accelerated evolution platform, chemically accelerated viral evolution (CAVE), which provides an effective and robust method for the rapid enhancement of desired bacteriophage characteristics. Here, our initial use of this methodology demonstrates its ability to confer significant improvements in phage thermal stability. Analysis of the mutation patterns that arise through CAVE iterations elucidates the manner in which specific genetic modifications bring forth desired changes in functionality, thereby providing a roadmap for bacteriophage engineering.
Volume
10
Issue
1
Language
English
OCDE Knowledge area
Biología celular, Microbiología
Scopus EID
2-s2.0-85089575979
PubMed ID
Source
Scientific Reports
ISSN of the container
2045-2322
Sponsor(s)
Structural?analysis?of?highly?mutable?proteins.? PDB files for the head-to-tail joining protein, tail-tubular protein A, and tail-tubular protein B were downloaded from the the structure of PDB ID: 6R21, which was published by Cuervo et al.24. Visualization and coloring of the structures was done at the Molecular Graphics and Computation Facility at the University of California, Berkeley, which is supported by the National Institute of Health, under award number S10OD023532.
Sources of information: Directorio de Producción Científica Scopus