Current challenges and future opportunities of phage therapy

FEMS Microbiology Reviews, Journal Year: 2020, Volume and Issue: 44(6), P. 684 - 700

Published: May 29, 2020

Antibiotic resistance is a major public health challenge worldwide, whose implications for global might be devastating if novel antibacterial strategies are not quickly developed. As natural predators of bacteria, (bacterio)phages may play an essential role in escaping such dreadful future. The rising problem antibiotic has revived the interest phage therapy and important developments have been achieved over last years. But where do we stand today what can expect from future? This question set to answer this review. Here, scour outcomes human clinical trials case reports, address barriers that way using phages settings. We particularly potential hinder discuss future avenues explore full capacity therapy.

Language: Английский

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Phage Therapy in the Resistance Era: Where Do We Stand and Where Are We Going?

Clinical Therapeutics, Journal Year: 2020, Volume and Issue: 42(9), P. 1659 - 1680

Published: Aug. 31, 2020

PurposeWidespread antibiotic-resistant bacteria are threatening the arsenal of existing antibiotics. Not only antibiotics less likely to be effective today, but their extensive use continues drive emergence multidrug-resistant pathogens. A new-old antibacterial strategy with bacteriophages (phages) is under development, namely, phage therapy. Phages targeted bacterial viruses multiple effector functions, which can reduce infections within human body. This review summarizes recent therapy clinical trials and patient cases outlines fundamentals behind treatment strategies mainly through bench-to-bedside approaches. We discuss challenges that remain in role phages when combined antibiotic therapy.MethodsThis narrative presents current knowledge latest findings regarding Relevant case reports research articles available Scopus PubMed databases discussed.FindingsAlthough data suggest tolerability and, some cases, efficacy therapy, functionality still requires careful definition. The lack well-controlled trial complex regulatory frameworks have driven most generation on a single-patient compassionate basis. These often include concomitant antibiotics, makes it difficult draw conclusions effectiveness alone. However, support using as potentiators resistance breakers; thus, adjuvants promising avenue for near-term development. Current gaps exist appropriate routes administration, selection, frequency dosage, resistance, pharmacokinetic pharmacodynamic properties phages. In addition, we highlight therapies mild adverse effects patients.ImplicationsAlthough more translational needed before implementation feasible, may well pivotal safeguarding humans against infections.

Language: Английский

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Bacteriophages as Alternatives to Antibiotics in Clinical Care

Antibiotics, Journal Year: 2019, Volume and Issue: 8(3), P. 138 - 138

Published: Sept. 4, 2019

Antimicrobial resistance is increasing despite new treatments being employed. With a decrease in the discovery rate of novel antibiotics, this threatens to take humankind back “pre-antibiotic era” clinical care. Bacteriophages (phages) are one most promising alternatives antibiotics for use. Although more than century mostly ad-hoc phage therapy has involved substantial experimentation, lack both regulatory guidance standards and effective execution trials meant that infectious bacterial diseases yet be widely adopted. However, several recent case studies show promise addressing these concerns. antibiotic crisis urgent search alternative infections, may soon fulfill its long-held promise. This review reports on applications various diseases, pharmacology, immunological responses phages, legal concerns, potential benefits disadvantages treatment.

Language: Английский

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Bacteriophage-host arm race: an update on the mechanism of phage resistance in bacteria and revenge of the phage with the perspective for phage therapy

Applied Microbiology and Biotechnology, Journal Year: 2019, Volume and Issue: 103(5), P. 2121 - 2131

Published: Jan. 24, 2019

Language: Английский

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Pharmacologically Aware Phage Therapy: Pharmacodynamic and Pharmacokinetic Obstacles to Phage Antibacterial Action in Animal and Human Bodies

Microbiology and Molecular Biology Reviews, Journal Year: 2019, Volume and Issue: 83(4)

Published: Oct. 29, 2019

The use of viruses infecting bacteria (bacteriophages or phages) to treat bacterial infections has been ongoing clinically for approximately 100 years. Despite that long history, the growing international crisis resistance standard antibiotics, abundant anecdotal evidence efficacy, and one successful modern clinical trial this phage therapy is not yet a mainstream approach in medicine.

Language: Английский

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Phage-Encoded Endolysins

Antibiotics, Journal Year: 2021, Volume and Issue: 10(2), P. 124 - 124

Published: Jan. 28, 2021

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions hydrolyze cell wall from within. There is significant evidence that proves ability degrade peptidoglycan externally without assistance phage. Thus, their incorporation therapeutic strategies opened new options for application against bacterial infections human and veterinary sectors, well within agricultural biotechnology sectors. While show promising results laboratory, it important document safety, immunogenicity in-vivo application. This review aims provide insights into synergy between antibiotics, formulation endolysins. provides crucial information clinical trials involving

Language: Английский

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Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: March 30, 2022

Bacteriophages (phages) may be used as an alternative to antibiotic therapy for combating infections caused by multidrug-resistant bacteria. In the last decades, there have been studies concerning use of phages and antibiotics separately or in combination both animal models well humans. The phenomenon phage-antibiotic synergy, which induce production bacterial hosts has observed. potential mechanisms phage synergy was presented this paper. Studies a biofilm model showed that with increase removal bacteria sequential treatment, consisting administration followed antibiotic, most effective eliminating biofilms. vivo predominantly show synergy. A few also describe antagonism indifference between antibiotics. Recent papers regarding application patients severe effectiveness simultaneous treatment antimicrobials on clinical outcome.

Language: Английский

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Coevolutionary phage training leads to greater bacterial suppression and delays the evolution of phage resistance

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(23)

Published: June 3, 2021

Significance The evolution of antibiotic-resistant bacteria threatens to claim over 10 million lives annually by 2050. This crisis has renewed interest in phage therapy, the use bacterial viruses treat infections. A major barrier successful therapy is that readily evolve resistance. One idea proposed combat resistance “training” phages using their natural capacity counter Here, we show training coevolving them with hosts for 1 mo repeatably enhances suppressing growth and delays emergence Enhanced suppression was caused several mechanisms, suggesting coevolutionary protocol produces a robust therapeutic employs complementary modes action.

Language: Английский

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Engineered phage with antibacterial CRISPR–Cas selectively reduce E. coli burden in mice

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(2), P. 265 - 274

Published: May 4, 2023

Abstract Antibiotic treatments have detrimental effects on the microbiome and lead to antibiotic resistance. To develop a phage therapy against diverse range of clinically relevant Escherichia coli , we screened library 162 wild-type (WT) phages, identifying eight phages with broad coverage E. complementary binding bacterial surface receptors, capability stably carry inserted cargo. Selected were engineered tail fibers CRISPR–Cas machinery specifically target . We show that bacteria in biofilms, reduce emergence phage-tolerant out-compete their ancestral WT coculture experiments. A combination four most bacteriophages, called SNIPR001, is well tolerated both mouse models minipigs reduces load gut better than its constituent components separately. SNIPR001 clinical development selectively kill which may cause fatal infections hematological cancer patients.

Language: Английский

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Phage-antibiotic combination is a superior treatment against Acinetobacter baumannii in a preclinical study

EBioMedicine, Journal Year: 2022, Volume and Issue: 80, P. 104045 - 104045

Published: May 7, 2022

Clinical phage therapy is often delivered alongside antibiotics. However, the phenomenon of phage-antibiotic synergy has been mostly studied in vitro. Here, we assessed vivo bactericidal effect a combination on Acinetobacter baumannii AB900 using øFG02, which binds to capsular polysaccharides and leads antimicrobial resensitisation vitro.We performed two-stage preclinical study murine model severe A. bacteraemia. In first stage, with an endpoint 11 h, mice (n = 4 per group) were treated either PBS, ceftazidime, or ceftazidime. The second stage involved only latter two groups 5 group), prolonged 16 h. primary outcome was average bacterial burden from four body sites (blood, liver, kidney, spleen). Bacterial colonies phage-treated retrieved screened for phage-resistance.In (CFU/g tissue) group (median: 4.55 × 105; interquartile range [IQR]: 2.79 105-2.81 106) significantly lower than PBS 2.42 109; IQR: 1.97 109-3.48 109) ceftazidime 3.86 108; 2.15 108-6.35 108), but not phage-only 1.28 107; 4.71 106-7.13 107). treatment 1.72 106; 5.11 105-4.00 outperformed 7.46 1.43 107-1.57 108). Phage-resistance emerged 96% animals receiving phages, all tested isolates 11) had loss-of-function mutations genes capsule biosynthesis increased sensitivity ceftazidime.øFG02 reliably drives evolution towards capsule-deficient, phage-resistant phenotype that resensitised This mechanism highlights clinical potential target restore antibiotic activity.National Health Medical Research Council (Australia).

Language: Английский

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