Bacteriophages: Protagonists of a Post-Antibiotic Era

The emergence of multi-drug-resistant bacteria represents a major public-health threat. Phages constitute a promising alternative to chemical antibiotics due to their high host specificity, abundance in nature, and evolvability. However, phage host specificity means that highly diverse bacterial species are particularly difficult to target for phage therapy. This is the case of Klebsiella pneumoniae, which presents a hypervariable extracellular matrix capsule exhibiting dozens of variants. Here, we report four novel phages infecting K. pneumoniae capsular type K22 which were isolated from environmental samples in Valencia, Spain. Full genome sequencing showed that these phages belong to the Podoviridae family and encode putative depolymerases that allow digestion of specific K22 K. pneumoniae capsules. Our results confirm the capsular type-specificity of K. pneumoniae phages, as indicated by their narrow infectivity in a panel of K. pneumoniae clinical isolates. Nonetheless, this work represents a step forward in the characterization of phage diversity, which may culminate in the future use of large panels of phages for typing and/or for combating multi-drug-resistant K. pneumoniae.

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“…In addition, the use of depolymerases in synergy with antibiotics has been proposed as a potent tool against Klebsiella sp. [21,22].…”

Section: Discussionmentioning

confidence: 99%

Isolation of Four Lytic Phages Infecting Klebsiella pneumoniae K22 Clinical Isolates from Spain

Domingo‐Calap

Beamud

Vienne

et al. 2020

IJMS

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“…phages), that is, viruses to bacteria, are regarded as a good choice in combating drug resistance due to its high efficiency and low mutation rates ( Hagens and Loessner, 2007 , Zhang and Buckling, 2012 ). In addition, phages show their great advantages over antibiotics in that they can usually kill just one species or strain, giving a more precise way to target pathogenic bacteria ( Domingo-Calap and Delgado-Martinez, 2018 ). In 2014, phage therapy was listed as one of seven promising solutions in the plan of US National Institute of Allergy and Infectious Diseases to counteract with antibiotic resistance ( Reardon, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Broad-host-range Salmonella bacteriophage STP4-a and its potential application evaluation in poultry industry

Lin

Jing

et al. 2020

Poultry Science

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Salmonella is regarded as the predominant cause of foodborne illnesses worldwide, and the increase of these antimicrobial-resistant strains makes it more difficult to prevent. On this occasion, bacteriophages (phages) stand out as an alternative biocontrol agent with high efficiency and low mutation rates. Salmonella phages have confronted challenges to counteract with more than 2,500 serovars of Salmonella spp. and overcome the universality of antibiotics to different species, and thus, broad-host-range phages infecting Salmonella spp. are urgently required to realize precise poultry treatment or clinical therapy. First, phage STP4-a was screened to have a broad host range through bioinformatics analysis, and then the host range assay proved that phage STP4-a could inhibit 88 out of 91 Salmonella strains. Then, in silico analysis excluded the possibility of phage STP4-a possessing any known lysogeny factors, toxins, pathogen-related genes, or foodborne allergens, and oral toxicity studies further ensured the safety of unknown factors or suspected risks. In addition, strong inhibition effects of phage STP4-a were seen on both single Salmonella strain and multiple Salmonella strains in vitro, reducing 3-5 log in 30 min. Phage STP4-a could survive and keep more than 50% activity in simulated stomach or intestine environments in vitro. In terms of antimicrobial activities in chickens, pretreatment with phage STP4-a was the most efficient approach to Salmonella biocontrol, non-detectable in feces during the 14-day experimental period. Therefore, phage STP4-a was an extremely broad-host-range and safe biocontrol agent, performing its potential as a food additive or therapeutic drug in poultry industry.

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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 .…”

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confidence: 99%

“…Despite the limitations described above, the antibacterial activities of bacteriophages are very attractive in combating the presence of unwanted bacteria. Hence, apart from employing them in the treatment of human diseases, the use of these viruses is also considered in food protection 7 , agriculture and industry 3 .…”

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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Bacteriophages: Protagonists of a Post-Antibiotic Era

Cited by 154 publications

References 80 publications

Isolation of Four Lytic Phages Infecting Klebsiella pneumoniae K22 Clinical Isolates from Spain

Isolation of Four Lytic Phages Infecting Klebsiella pneumoniae K22 Clinical Isolates from Spain

Broad-host-range Salmonella bacteriophage STP4-a and its potential application evaluation in poultry industry

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

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