Genetic and Chemical Engineering of Phages for Controlling Multidrug-Resistant Bacteria

Abstract

Along with the excessive use of antibiotics, the emergence and spread of multidrug-resistant bacteria has become a public health problem and a great challenge vis-à-vis the control and treatment of bacterial infections. As the natural predators of bacteria, phages have reattracted researchers’ attentions. Phage therapy is regarded as one of the most promising alternative strategies to fight pathogens in the post-antibiotic era. Recently, genetic and chemical engineering methods have been applied in phage modification. Among them, genetic engineering includes the expression of toxin proteins, modification of host recognition receptors, and interference of bacterial phage-resistant pathways. Chemical engineering, meanwhile, involves crosslinking phage coats with antibiotics, antimicrobial peptides, heavy metal ions, and photothermic matters. Those advances greatly expand the host range of phages and increase their bactericidal efficiency, which sheds light on the application of phage therapy in the control of multidrug-resistant pathogens. This review reports on engineered phages through genetic and chemical approaches. Further, we present the obstacles that this novel antimicrobial has incurred.

Bacterial Biofilm Destruction: A Focused Review On The Recent Use of Phage-Based Strategies With Other Antibiofilm Agents

“… 70 Some temperate phages with non-lytic features are genetically engineered into lytic phages with the production of endolysins useful for biofilm destruction and removal. 71 With about half of the sequenced bacteria being lysogens, temperate phages could be easier to find than isolating lytic phages from nature. 72 …”

“…70 Some temperate phages with non-lytic features are genetically engineered into lytic phages with the production of endolysins useful for biofilm destruction and removal. 71 With about half of the sequenced bacteria being lysogens, temperate phages could be easier to find than isolating lytic phages from nature. 72 In a recent study, endolysin PM-477 of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages when recombinantly expressed, demonstrated strong bactericidal activity against four different Gardnerella species.…”

Phages against Pathogenic Bacterial Biofilms and Biofilm-Based Infections: A Review

“…There has been renewed interest in phage therapy in the past few years amid the emergence of antibiotic-resistant bacteria and a global supply shortage of newly developed antibiotics [9]. Recent studies have shown that phage therapy can be one of the most promising alternative treatment options for antibiotic-resistant pathogens, which is more effective than antibiotics against bacterial infections [10].…”

An Engineered λ Phage Enables Enhanced and Strain-Specific Killing of Enterohemorrhagic Escherichia coli

“…In addition, phages have been used to remove pathogens from foods ( 17 , 18 ) and crops ( 19 ). However, limitations exist in the use of phages as an antimicrobial agent (AMA), including low efficiency in killing the target bacteria and quickly developing resistance by the host ( 20 ). To enhance the killing efficacy, researchers have developed many strategies, including the use of multiple phages (known as cocktails) for the same targets and engineered phages carrying host-targeting CRISPR spacers or even whole CRISPR-Cas systems ( 20 – 24 ).…”

“…However, limitations exist in the use of phages as an antimicrobial agent (AMA), including low efficiency in killing the target bacteria and quickly developing resistance by the host ( 20 ). To enhance the killing efficacy, researchers have developed many strategies, including the use of multiple phages (known as cocktails) for the same targets and engineered phages carrying host-targeting CRISPR spacers or even whole CRISPR-Cas systems ( 20 – 24 ). The latter strategy, also known as “sequence-specific” killing, uses the sequences incorporated as CRISPR spacers to guide the specificity of the targets and thus can be adapted to kill either a particular strain by using the strain-specific sequences as the spacers or a species by using the conserved sequences across its multiple strains.…”