Phage therapy: Current status and perspectives

Górski, Andrzej; Międzybrodzki, Ryszard; Węgrzyn, Grzegorz; Jończyk‐Matysiak, Ewa; Borysowski, Jan; Weber‐Dąbrowska, Beata

doi:10.1002/med.21593

Cited by 108 publications

(87 citation statements)

References 16 publications

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“…However, the recent awareness of antagonism has propelled some in vitro assessment of phageantibiotic action prior to treatment to select for synergistic combinations, a personalized approach that has led to satisfactory therapeutic outcomes (15,16). Several phage-antibiotic combinations have been investigated in vitro and in vivo in multiple bacterial species (17,18) but there have been mixed results with combinatorial treatment (13,19,20). For instance, quinolones can be synergistic with phages against P. aeruginosa in one study while antagonistic in another (21,22).…”

Section: Five Years Later In 2019 the Centers For Disease Control Anmentioning

confidence: 99%

Phage-Antibiotic Synergy is Driven by a Unique Combination of Antibacterial Mechanism of Action and Stoichiometry

Liu

Green

Min

et al. 2020

Preprint

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The continued rise in antibiotic resistance is precipitating a medical crisis. Bacteriophage (phage) has been hailed as one possible therapeutic option to augment the efficacy of antibiotics.However, only a handful of studies have addressed the synergistic relationship between phage and antibiotics. Here, we report a comprehensive analysis of phage-antibiotic interaction that evaluates synergism, additivism, and antagonism for all classes of antibiotics across clinically achievable stoichiometries. We combined an optically-based real-time microtiter plate readout with a matrix-like heatmap of treatment potencies to measure phage and antibiotic synergy (PAS), a process we term synography. Phage-antibiotic synography was performed against a pandemic drug-resistant clonal group of E. coli (ExPEC) with antibiotic levels blanketing the minimum inhibitor concentration (MIC) across seven orders of viral titers. Our results suggest that, under certain conditions, phages provide an adjuvating effect by lowering the MIC for drugresistant strains. Furthermore, synergistic and antagonistic interactions are highly dependent on the mechanism of bacterial inhibition by the class of antibiotic paired to the phage, and when synergism is observed, it suppresses the emergence of resistant cells. Host conditions that simulate the infection environment, including serum and urine, suppress PAS in a bacterial growth-dependent manner. Lastly, phage burst size seems to be a significant driver of synergism.Collectively, this data suggests lytic phages can resuscitate an ineffective antibiotic for previously resistant bacteria, while also synergize with antibiotics in a class-dependent manner, processes that may be dampened by lower bacterial growth rates found in host environments. Significance StatementBacteriophage (phage) therapy is a promising approach to combat the rise of multi-drug resistant bacteria. Currently, the preferred clinical modality is to pair phage with an antibiotic, a practice thought to improve efficacy. However, antagonism between phage and antibiotics has been reported, the choice of phage and antibiotic is not often empirically determined, and the effect of the host factors on the effectiveness is unknown. Here, we interrogate phage-antibiotic interactions across antibiotics with different mechanisms of action. Our results suggest that phage can lower the working MIC for bacterial strains already resistant to the antibiotic, is dependent on the antibiotic class and stoichiometry of the pairing, and is dramatically influenced by the host microenvironment.

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Section: Five Years Later In 2019 the Centers For Disease Control Anmentioning

confidence: 99%

Phage-Antibiotic Synergy is Driven by a Unique Combination of Antibacterial Mechanism of Action and Stoichiometry

Liu

Green

Min

et al. 2020

Preprint

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“…When considering phage therapy as an alternative treatment of human and animal infectious diseases, some conditions and requirements appear crucial [ 6 , 7 , 8 ]. Firstly, a large collection of phages infecting various bacterial species and strains must be established to offer an effective means of treatment of patients or animals suffering from diseases caused by different bacteria.…”

Section: Introductionmentioning

confidence: 99%

“…Thirdly, phages used in therapeutic approaches should not bear genes coding for toxins or other agents which are deleterious for humans and animals. These requirements indicate that isolation and detailed characterization of many bacteriophages is necessary to develop potentially effective phage therapy procedures [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Characteristics of a Series of Three Bacteriophages Infecting Salmonella enterica Strains

Kosznik-Kwaśnicka

Ciemińska

Grabski

et al. 2020

IJMS

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Molecular and functional characterization of a series of three bacteriophages, vB_SenM-1, vB_SenM-2, and vB_SenS-3, infecting various Salmonella enterica serovars and strains is presented. All these phages were able to develop lytically while not forming prophages. Moreover, they were able to survive at pH 3. The phages revealed different host ranges within serovars and strains of S. enterica, different adsorption rates on host cells, and different lytic growth kinetics at various temperatures (in the range of 25 to 42 °C). They efficiently reduced the number of cells in the bacterial biofilm and decreased the biofilm mass. Whole genome sequences of these phages have been determined and analyzed, including their phylogenetic relationships. In conclusion, we have demonstrated detailed characterization of a series of three bacteriophages, vB_SenM-1, vB_SenM-2, and vB_SenS-3, which reveal favorable features in light of their potential use in phage therapy of humans and animals, as well as for food protection purposes.

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“…The appearance of multidrug-resistant bacterial strains, particularly human pathogens, is one of the major problems of current medicine 1 . Bacteriophage therapy (or phage therapy) is one possible alternative to treat bacterial infections [2][3][4][5] . This potential therapeutic option is based on the assumption that bacteriophages, i.e., viruses that can destroy bacterial cells, can infect and eliminate bacterial pathogens in humans or animals 5 .…”

mentioning

confidence: 99%

“…Bacteriophage therapy (or phage therapy) is one possible alternative to treat bacterial infections [2][3][4][5] . This potential therapeutic option is based on the assumption that bacteriophages, i.e., viruses that can destroy bacterial cells, can infect and eliminate bacterial pathogens in humans or animals 5 . Bacteriophages are usually specific to a single bacterial species, or even strain, and they are able to propagate only if specific host bacteria are available.…”

mentioning

confidence: 99%

Characterization of a bacteriophage, vB_Eco4M-7, that effectively infects many Escherichia coli O157 strains

Necel

Bloch

Nejman-Faleńczyk

et al. 2020

Sci Rep

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The characterization of a recently isolated bacteriophage, vB_Eco4M-7, which effectively infects many, though not all, Escherichia coli O157 strains, is presented. The genome of this phage comprises doublestranded DNA, 68,084 bp in length, with a GC content of 46.2%. It contains 96 putative open reading frames (ORFs). Among them, the putative functions of only 35 ORFs were predicted (36.5%), whereas 61 ORFs (63.5%) were classified as hypothetical proteins. The genome of phage vB_Eco4M-7 does not contain genes coding for integrase, recombinase, repressors or excisionase, which are the main markers of temperate viruses. Therefore, we conclude that phage vB_Eco4M-7 should be considered a lytic virus. This was confirmed by monitoring phage lytic development by a one-step growth experiment. Moreover, the phage forms relatively small uniform plaques (1 mm diameter) with no properties of lysogenization. Electron microscopic analyses indicated that vB_Eco4M-7 belongs to the Myoviridae family. Based on mass spectrometric analyses, including the fragmentation pattern of unique peptides, 33 phage vB_Eco4M-7 proteins were assigned to annotated open reading frames. Importantly, genome analysis suggested that this E. coli phage is free of toxins and other virulence factors. In addition, a similar, previously reported but uncharacterized bacteriophage, ECML-117, was also investigated, and this phage exhibited properties similar to vB_Eco4M-7. Our results indicate that both studied phages are potential candidates for phage therapy and/or food protection against Shiga toxin-producing E. coli, as the majority of these strains belong to the O157 serotype.

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Phage therapy: Current status and perspectives

Cited by 108 publications

References 16 publications

Phage-Antibiotic Synergy is Driven by a Unique Combination of Antibacterial Mechanism of Action and Stoichiometry

Phage-Antibiotic Synergy is Driven by a Unique Combination of Antibacterial Mechanism of Action and Stoichiometry

Characteristics of a Series of Three Bacteriophages Infecting Salmonella enterica Strains

Characterization of a bacteriophage, vB_Eco4M-7, that effectively infects many Escherichia coli O157 strains

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