Researchers are investigating bacteriophage treatments

In a recently published study Cellresearchers presented an overview of bacteriophage therapy, including mechanisms, types, design, and applications of bacteriophage therapy.

Research: Phage therapy: from biological mechanisms to future directions. Image credit: Tatyana Shepeleva/Shutterstock

Antimicrobial resistance (AMR) has been associated with significant morbidity and mortality globally, particularly in low-income countries, and the incidence of AMR increased during the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The continued increase in AMR cases has reignited research into substitutes, one promising avenue being treatment with bacteriophages.

About the exam

In the current review, researchers provide an overview of bacteriophage therapy, including mechanisms, design, and applications.

Introduction to bacteriophage biology

Bacteriophages (Greek for “bacteria eater”) are naturally occurring bacterial predators that have co-evolved with bacterial organisms over billions of years. First used by Félix d’Hérelle in 1917 to treat bacterial dysentery in children, bacteriophage therapy was widely used to treat bacterial infections in animals and humans before the use of penicillin.

Bacteriophages are viruses capable of replicating within the host, possessing small genomes, extensive use of the host machinery for replication, and host cell specificity. Bacteriophages require bacteria to express specific molecules on the surface to which the bacteriophage binds, and they do not induce host defenses that could inactivate the bacteriophage upon entry.

The most commonly observed virion morphology includes double-stranded deoxyribonucleic acid (dsDNA) tailed bacteriophages in which the deoxyribonucleic acid is located in a head- or tail-linked capsid. Infection begins with binding of the tail end to the bacterial cell wall and genomic insertion of the head/capsid into the cytoplasm through the cell membrane. The head and tail of the protein do not enter cells.

Most bacteriophages are either mild or lytic. Lytic-type phages kill a very high percentage of the bacterial cells they infect and are therefore used as therapeutic agents. Upon infection, the lytic type of bacteriophage executes a developmental program that includes gene expression in the primary phage, genomic replication, late expression and gene fusion of the bacteriolytic virion structure, assembly of packaged particles, and finally lysis. bacteria. Phages are genomically very diverse, and phage genomes are densely packed with overlapping protein- and/or ribonucleic acid (RNA)-coding genes and populated by small UKF genes (unknown function).

Bacteriophage genomes are ubiquitous mosaics containing single genes (or subsets of genes) in different genomic contexts in otherwise unrelated bacteriophages. Therapeutic bacteriophages include bacteriophages, Muddy and Maestro, which are used to treat infections. Mycobacterium abscessus infections and Acinetobacter baumanniiaccording to.

Design and application of bacteriophage therapy

Phages can occur naturally or be genetically modified. Environmental or natural phages can be found wherever bacterial hosts exist, including lakes, oceans, animals, plants, and soil. Phages can be genetically engineered to allow programmed and functional organization of bacteriophage particles for greater biofilm penetration by targeting intracellular pathogens or to improve pharmacodynamic and/or pharmacokinetic properties.

Phage genome engineering involves the construction of modified phages and the recovery of the desired progeny from a pool of parenteral strains. Homologous genome engineering methods are used to live By counterselection based on the CRISPR (short regularly interspaced palindromic repeat)-Cas (CRISPR-associated protein) system. The method of homologous genetic recombination consists of the recombination of phage DNA with the homologous region of plasmid deoxyribonucleic acid. invivo Phage genetic engineering involves recombination of the phage genome and electroporated products of polymerase chain reaction (PCR) analysis with homologous arms.

The BRED technique (bacteriophage recombination of electroporated DNA) consists of the recombination of co-electroporated phage deoxyribonucleic acid and PCR analysis products with homologous arms. Subsequently, reverse selection of RNA-directed ribonucleic acid nucleases (Cas13) or RNA-directed deoxyribonucleic acid nucleases (Cas9,12) is applied to selectively eliminate unmodified bacteriophages.

Construction of synthetic genomes allows construction of genomes by design by combining bacteriophage genome fragments amplified by PCR analysis and synthetic oligonucleotides. Synthetic bacteriophage genomes are fused into a vector in vitro or a yeast-based compound. Subsequently, the assembled genomes are “rebooted” using cell-free TXTL (transcription-translation) systems or appropriate bacteria.

Bacteriophage therapy has been used to treat infections associated with implanted devices and lung infections, followed by prostatitis, burns, endocarditis, intra-abdominal infections, disseminated infections, urinary tract infections, osteomyelitis, and skin infections. For humans, phage can be used as a vector for biodefense to deliver vaccines or treatments, for example to detect pathogens. Bacillus anthracis or Yersinia pestisprevention during epidemics (e.g. Vibrio plague and Mycobacterium tuberculosis) and microbiome preparation.

Phage can also be used in veterinary medicine Salmonella, E.coliand Campylobacter infections and to replace antibiotics in animal husbandry. Environmental applications include wastewater disinfection, food safety, and antibiotic replacement in aquaculture and agriculture.

In conclusion, according to the results of the study, phage therapy may be an effective alternative to antibiotic therapy for the treatment of bacterial infections. Therapeutic bacteriophages must be lytic, effectively kill the bacterial host, and be fully characterized to exclude side effects. Phage therapy is usually given intravenously and is considered safe; however, adaptive immunological responses to bacteriophages may compromise therapeutic efficacy.

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