The resurgence of phage-based therapy in the era of increasing antibiotic resistance: From research progress to challenges and prospects

Anyaegbunam, Ngozi Joannes; Anekpo, Chijioke C.; Anyaegbunam, Zikora Kizito Glory; Doowuese, Yandev; Chinaka, Chinwe Blessing; Odo, Oluchi Joannes; Sharndama, Hyelnaya Cletus; Okeke, Onyekachi Philomena; Elibe, Ifeanyi

doi:10.1016/j.micres.2022.127155

Cited by 28 publications

(18 citation statements)

References 155 publications

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“…The synergistic effect of phages can be achieved by combining phages with some biomaterials. 20 T7 phage library was screened for its affinity toward K-Ras (Growth driver and efficient drug target of various kinds of tumors) and showed 10 times more affinity toward the target K-Ras than wild-type inhibitory phages. The surface plasma resonance method is used to measure polypeptide binding abilities to K-Ras.…”

Section: Phage Application Using Recombinant Dna (Rdna) Technologymentioning

confidence: 99%

“…This process is termed "Immunophage Synergy," in which phage administration elicits immune responses against bacteria and not against phages. 20 However, the human immune response study is vast, and every individual may respond differently to phage treatment. In this scenario, pharmacokinetics helps by preparing phage cocktails or formulations personalized to the infected individual.…”

Section: Immunogenic Responses During Phage Therapymentioning

confidence: 99%

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Bacteriophages as a potential substitute for antibiotics: A comprehensive review

Kushwaha,

Sahu,

Yadav

et al. 2024

Cell Biochemistry & Function

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Over the years, the administration of antibiotics for the purpose of addressing bacterial infections has become increasingly challenging due to the increased prevalence of antimicrobial resistance exhibited by various strains of bacteria. Multidrug‐resistant (MDR) bacterial species are rising due to the unavailability of novel antibiotics, leading to higher mortality rates. With these conditions, there is a need for alternatives in which phage therapy has made promising results. Phage‐derived endolysins, phage cocktails, and bioengineered phages are effective and have antimicrobial properties against MDR and extensively drug‐resistant strains. Despite these, it has been observed that phages can give antimicrobial activity to more than one bacterial species. Thus, phage cocktail against resistant strains provides broad spectrum treatment and magnitude of effectivity, which is many folds higher than antibiotics. Many commercially available endolysins such as Staphefekt SA.100, Exebacase (CF‐301), and N‐Rephasin®SAL200 are used in biofilm penetration and treating plant diseases. The role of CMP1 phage endolysin in transgenic tomato plants in preventing Clavibacter michiganensis infection and the effectiveness of phage in protecting Atlantic salmon from vibriosis have been reported. Furthermore, phage‐derived endolysin therapy, such as TSPphg phage exogenous treatment, can aid in disrupting cell walls, leading to bacterial cell lysis. As animals in aquaculture and slaughterhouses are highly susceptible to bacterial infections, effective phage therapy instead of antibiotics can help treat poultry animals, preserve them, and facilitate disease‐free trade. Using bioengineered phages and phage cocktails enhances the effectiveness by providing a broad spectrum of phages and target specificity. Research is currently being conducted on clinical trials to confirm the efficacy of engineered phages and phage cocktails in humans. Although obtaining commercial approval may be time‐consuming, it will be beneficial in the postantibiotic era. This review provides an overview of the significance of phage therapy as a potential alternative to antibiotics in combating resistant bacterial strains and its application to various fields and emphasizes the importance of safeguarding and ensuring treatment efficacy.

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Section: Phage Application Using Recombinant Dna (Rdna) Technologymentioning

confidence: 99%

Section: Immunogenic Responses During Phage Therapymentioning

confidence: 99%

Bacteriophages as a potential substitute for antibiotics: A comprehensive review

Kushwaha,

Sahu,

Yadav

et al. 2024

Cell Biochemistry & Function

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“…Several alternative therapies are currently in use in clinical settings, while others are still undergoing clinical trials [11]. Some of the emerging approaches for combating resistant pathogens are listed as follows: (1) combinatorial therapy (combination of different antibiotics or with adjuvants); (2) the use of antimicrobial peptides either in single or in combination with antibiotics; (3) bacteriophage therapy; (4) antibacterial antibodies; (5) use of phytochemicals; (6) use of nanoparticles/nanomaterials either in their single form or in combination with antibiotics and (7) photothermal light therapy [12][13][14][15][16][17][18] (Figure 1). Despite all these emerging approaches, vaccines offer a more reliable potential for curbing and reducing the drug-resistant infectious disease crisis.…”

Section: Introductionmentioning

confidence: 99%

Vaccine development for bacterial pathogens: Advances, challenges and prospects

Elibe

Sharndama

Anyaegbunam

et al. 2023

Tropical Med Int Health

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The advent and use of antimicrobials have played a key role in treating potentially life-threatening infectious diseases, improving health, and saving the lives of millions of people worldwide. However, the emergence of multidrug resistant (MDR) pathogens has been a significant health challenge that has compromised the ability to prevent and treat a wide range of infectious diseases that were once treatable. Vaccines offer potential as a promising alternative to fight against antimicrobial resistance (AMR) infectious diseases. Vaccine technologies include reverse vaccinology, structural biology methods, nucleic acid (DNA and mRNA) vaccines, generalised modules for membrane antigens, bioconjugates/glycoconjugates, nanomaterials and several other emerging technological advances that are offering a potential breakthrough in the development of efficient vaccines against pathogens. This review covers the opportunities and advancements in vaccine discovery and development targeting bacterial pathogens. We reflect on the impact of the already-developed vaccines targeting bacterial pathogens and the potential of those currently under different stages of preclinical and clinical trials. More importantly, we critically and comprehensively analyse the challenges while highlighting the key indices for future vaccine prospects. Finally, the issues and concerns of AMR for low-income countries (sub-Saharan Africa) and the challenges with vaccine integration, discovery and development in this region are critically evaluated. K E Y W O R D Santimicrobial resistant bacteria, bacterial vaccines, emerging vaccine technologies, infectious diseases, lowand middle-income countries, vaccines

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“…Given the rising incidence of multidrug-resistant (MDR) bacterial pathogens, bacteriophages (phages) are becoming a focus of interest for treating infectious diseases [ 1 , 2 ]. Ventilator-associated pneumonia (VAP), one of the most common nosocomial infections in ventilated patients with a high risk of mortality, is caused mainly by MDR-bacteria [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Repetitive Exposure to Bacteriophage Cocktails against Pseudomonas aeruginosa or Escherichia coli Provokes Marginal Humoral Immunity in Naïve Mice

Weissfuss

Wienhold

Bürkle

et al. 2023

Viruses

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Phage therapy of ventilator-associated pneumonia (VAP) is of great interest due to the rising incidence of multidrug-resistant bacterial pathogens. However, natural or therapy-induced immunity against therapeutic phages remains a potential concern. In this study, we investigated the innate and adaptive immune responses to two different phage cocktails targeting either Pseudomonas aeruginosa or Escherichia coli—two VAP-associated pathogens—in naïve mice without the confounding effects of a bacterial infection. Active or UV-inactivated phage cocktails or buffers were injected intraperitoneally daily for 7 days in C57BL/6J wild-type mice. Blood cell analysis, flow cytometry analysis, assessment of phage distribution and histopathological analysis of spleens were performed at 6 h, 10 days and 21 days after treatment start. Phages reached the lungs and although the phage cocktails were slightly immunogenic, phage injections were well tolerated without obvious adverse effects. No signs of activation of innate or adaptive immune cells were observed; however, both active phage cocktails elicited a minimal humoral response with secretion of phage-specific antibodies. Our findings show that even repetitive injections lead only to a minimal innate and adaptive immune response in naïve mice and suggest that systemic phage treatment is thus potentially suitable for treating bacterial lung infections.

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The resurgence of phage-based therapy in the era of increasing antibiotic resistance: From research progress to challenges and prospects

Cited by 28 publications

References 155 publications

Bacteriophages as a potential substitute for antibiotics: A comprehensive review

Bacteriophages as a potential substitute for antibiotics: A comprehensive review

Vaccine development for bacterial pathogens: Advances, challenges and prospects

Repetitive Exposure to Bacteriophage Cocktails against Pseudomonas aeruginosa or Escherichia coli Provokes Marginal Humoral Immunity in Naïve Mice

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