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Genetically Engineered Phages: a Review of Advances over the Last Decade

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TLDR
This review highlights advances in techniques used to engineer phages as vehicles for drug delivery and vaccines, as well as for the assembly of new materials, and discusses existing challenges and opportunities.
Abstract
Soon after their discovery in the early 20th century, bacteriophages were recognized to have great potential as antimicrobial agents, a potential that has yet to be fully realized. The nascent field of phage therapy was adversely affected by inadequately controlled trials and the discovery of antibiotics. Although the study of phages as anti-infective agents slowed, phages played an important role in the development of molecular biology. In recent years, the increase in multidrug-resistant bacteria has renewed interest in the use of phages as antimicrobial agents. With the wide array of possibilities offered by genetic engineering, these bacterial viruses are being modified to precisely control and detect bacteria and to serve as new sources of antibacterials. In applications that go beyond their antimicrobial activity, phages are also being developed as vehicles for drug delivery and vaccines, as well as for the assembly of new materials. This review highlights advances in techniques used to engineer phages for all of these purposes and discusses existing challenges and opportunities for future work.

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Journal ArticleDOI

Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies

TL;DR: The mechanism of antibiotic resistance in P. aeruginosa is a recently characterized mechanism, which includes biofilm-mediated resistance and formation of multidrug-tolerant persister cells, and is responsible for recalcitrance and relapse of infections.
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Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches.

TL;DR: The latest information on therapeutic use of fecal microbial transplantation is summarized and improved strategies to selectively normalize the dysbiotic microbiome in personalized approaches to treatment are proposed.
Journal ArticleDOI

Phage Therapy: A Renewed Approach to Combat Antibiotic-Resistant Bacteria.

TL;DR: How the modern scientific community works to improve the reliability and success ofphage therapy in the clinic is explored and how to properly evaluate the potential for phage therapy to combat antibiotic-resistant bacteria is discussed.
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Alternatives to Conventional Antibiotics in the Era of Antimicrobial Resistance

TL;DR: A review of the various promising approaches that have been adopted in the search for therapies that can substitute for antibiotics, including genetically modified phages, antibacterial oligonucleotides, and CRISPR-Cas9.
Journal ArticleDOI

Formation, physiology, ecology, evolution and clinical importance of bacterial persisters.

TL;DR: This work defines persistence, summarizes the various aspects of persister physiology and shows their heterogeneous nature, and focuses on the role of key cellular processes and mechanisms controlling the formation of a subpopulation of tolerant cells.
References
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Journal ArticleDOI

Bacterial biofilms : A common cause of persistent infections

TL;DR: Improvements in understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
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CRISPR provides acquired resistance against viruses in prokaryotes

TL;DR: It is found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences, and CRISPR provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity.
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Next-generation DNA sequencing.

TL;DR: Next-generation DNA sequencing has the potential to dramatically accelerate biological and biomedical research, by enabling the comprehensive analysis of genomes, transcriptomes and interactomes to become inexpensive, routine and widespread, rather than requiring significant production-scale efforts.
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Origins and Evolution of Antibiotic Resistance

TL;DR: A review of antibiotic resistance development over the past half-century can be found in this article, with the oft-restated conclusion that it is time to act and to restore the therapeutic applications of antibiotics.
Journal ArticleDOI

Antibacterial resistance worldwide: causes, challenges and responses.

TL;DR: The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics, and today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance.
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