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Molecular biology reports
Aug, 2023;50 (8): 7055-7067.

Bacteriophage genome engineering for phage therapy to combat bacterial antimicrobial resistance as an alternative to antibiotics.

Sani Sharif Usman, Abdullahi Ibrahim Uba, Evangeline Christina
Author Information
  1. Sani Sharif Usman: Department of Molecular Biology and Genetic Engineering, School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144401, Punjab, India.
  2. Abdullahi Ibrahim Uba: Department of Molecular Biology and Genetics, Istanbul AREL University, 34537, Istanbul, Türkiye.
  3. Evangeline Christina: Department of Molecular Biology and Genetic Engineering, School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar-Delhi G.T. Road, Phagwara, 144401, Punjab, India. evangeline.23827@lpu.co.in. ORCID
PMID: 37392288 DOI: 10.1007/s11033-023-08557-4

Abstract

Bacteriophages (phages) are viruses that mainly infect bacteria and are ubiquitously distributed in nature, especially to their host. Phage engineering involves nucleic acids manipulation of phage genome for antimicrobial activity directed against pathogens through the applications of molecular biology techniques such as synthetic biology methods, homologous recombination, CRISPY-BRED and CRISPY-BRIP recombineering, rebooting phage-based engineering, and targeted nucleases including CRISPR/Cas9, zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). Management of bacteria is widely achieved using antibiotics whose mechanism of action has been shown to target both the genetic dogma and the metabolism of pathogens. However, the overuse of antibiotics has caused the emergence of multidrug-resistant (MDR) bacteria which account for nearly 5 million deaths as of 2019 thereby posing threats to the public health sector, particularly by 2050. Lytic phages have drawn attention as a strong alternative to antibiotics owing to the promising efficacy and safety of phage therapy in various models in vivo and human studies. Therefore, harnessing phage genome engineering methods, particularly CRISPR/Cas9 to overcome the limitations such as phage narrow host range, phage resistance or any potential eukaryotic immune response for phage-based enzymes/proteins therapy may designate phage therapy as a strong alternative to antibiotics for combatting bacterial antimicrobial resistance (AMR). Here, the current trends and progress in phage genome engineering techniques and phage therapy are reviewed.

Keywords

Antibiotics Antimicrobial resistance CRISPR/Cas9 Enzybiotics Global mortality Lytic bacteriophages Multidrug-resistant bacteria Phage engineering

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MeSH Term

Humans
Anti-Bacterial Agents
Bacteriophages
Phage Therapy
Drug Resistance, Bacterial
Bacteria
Bacterial Infections

Chemicals

Anti-Bacterial Agents
Journal Article Review
Article has an altmetric score of 6

Word Cloud

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