Bacteriophages and bacteriophage-derived endolysins as potential therapeutics to combat Gram-positive spore forming bacteria

Nakonieczna, Aleksandra; Cooper, Callum; Gryko, Romuald

doi:10.1111/jam.12881

Cited by 43 publications

(34 citation statements)

References 102 publications

(154 reference statements)

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“…Examples include applications for use of the phages ListShield (Intralytix, Inc., Baltimore, MD) for Listeria monocytogenes and EcoShield (Intralytix) for Escherichia coli O157:H7 to protect against foodborne disease (23,24). In addition, not only phage but also phage endolysin, which is used at the end of the phage lytic cycle, is being assessed for therapeutic use (25). The quick approval of more applications of phage therapy for bacterial infections that are hard to be treated is strongly expected.…”

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confidence: 99%

Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis

Furusawa

Iwano

Hiyashimizu

et al. 2016

Appl Environ Microbiol

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Bacterial keratitis of the horse is mainly caused by staphylococci, streptococci, and pseudomonads. Of these bacteria, Pseudomonas aeruginosa sometimes causes rapid corneal corruption and, in some cases, blindness. Antimicrobial resistance can make treatment very difficult. Therefore, new strategies to control bacterial infection are required. A bacteriophage (phage) is a virus that specifically infects and kills bacteria. Since phage often can lyse antibiotic-resistant bacteria because the killing mechanism is different, we examined the use of phage to treat horse bacterial keratitis. We isolated Myoviridae or Podoviridae phages, which together have a broad host range. They adsorb efficiently to host bacteria; more than 80% of the ⌽R18 phage were adsorbed to host cells after 30 s. In our keratitis mouse model, the administration of phage within 3 h also could kill bacteria and suppress keratitis. A phage multiplicity of infection of 100 times the host bacterial number could kill host bacteria effectively. A cocktail of two phages suppressed bacteria in the keratitis model mouse. These data demonstrated that the phages in this study could completely prevent the keratitis caused by P. aeruginosa in a keratitis mouse model. Furthermore, these results suggest that phage may be a more effective prophylaxis for horse keratitis than the current preventive use of antibiotics. Such treatment may reduce the use of antibiotics and therefore antibiotic resistance. Further studies are required to assess phage therapy as a candidate for treatment of horse keratitis. IMPORTANCEAntibiotic-resistant bacteria are emerging all over the world. Bacteriophages have great potential for resolution of this problem. A bacteriophage, or phage, is a virus that infects bacteria specifically. As a novel therapeutic strategy against racehorse keratitis caused by Pseudomonas aeruginosa, we propose the application of phages for treatment. Phages isolated in this work had in vitro effectiveness for a broad range of P. aeruginosa strains. Indeed, a great reduction of bacterial proliferation was shown in phage therapy for mouse models of P. aeruginosa keratitis. Therefore, to reduce antibiotic usage, phage therapy should be investigated and developed further.

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confidence: 99%

Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis

Furusawa

Iwano

Hiyashimizu

et al. 2016

Appl Environ Microbiol

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“…). This gene, together with their neighbour holins and the transmembrane proteins, resemble the lysis cassettes described in Bacillus (Nakonieczna et al ., ). Therefore, due to the high specificity of these lytic enzymes, it is very likely that these five contigs belong to temperate phages of Pontibacillus , for which no virus has been reported yet in the literature.…”

Section: Resultsmentioning

confidence: 97%

Prokaryotic and viral community of the sulfate‐rich crust from Peñahueca ephemeral lake, an astrobiology analogue

Martín-Cuadrado

Senel

Martínez‐García

et al. 2019

Environmental Microbiology

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Summary Peñahueca is an athalassohaline hypersaline inland ephemeral lake originated under semiarid conditions in the central Iberian Peninsula (Spain). Its chemical composition makes it extreme for microbial life as well as a terrestrial analogue of other planetary environments. To investigate the persistence of microbial life associated with sulfate‐rich crusts, we applied cultivation‐independent methods (optical and electron microscopy, 16S rRNA gene profiling and metagenomics) to describe the prokaryotic community and its associated viruses. The diversity for Bacteria was very low and was vastly dominated by endospore formers related to Pontibacillus marinus of the Firmicutes phylum. The archaeal assemblage was more diverse and included taxa related to those normally found in hypersaline environments. Several ‘metagenome assembled genomes’ were recovered, corresponding to new species of Pontibacillus, several species from the Halobacteria and one new member of the Nanohaloarchaeota. The viral assemblage, although composed of the morphotypes typical of high salt systems, showed little similarity to previously isolated/reconstructed halophages. Several putative prophages of Pontibacillus and haloarchaeal hosts were identified. Remarkably, the Peñahueca sulfate‐rich metagenome contained CRISPR‐associated proteins and repetitions which were over 10‐fold higher than in most hypersaline systems analysed so far.

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“…Notably, they have less bacterial resistance issues than antibiotics [84] and seem to be effective as decontamination reagents [83]. Moreover, resistance development to endolysin catalytic activity is unlikely as there are no described cases of bacteria-losing sensitivity to these enzymes or resistant mutants obtained after in vitro exposure to sublethal concentrations of protein [122]. …”

Section: Phage-derived Proteins As Antibacterial Agentsmentioning

confidence: 99%

Bacteriophages and Their Immunological Applications against Infectious Threats

Criscuolo

Spadini

Lamanna

et al. 2017

Journal of Immunology Research

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Bacteriophage therapy dates back almost a century, but the discovery of antibiotics led to a rapid decline in the interests and investments within this field of research. Recently, the novel threat of multidrug-resistant bacteria highlighted the alarming drop in research and development of new antibiotics: 16 molecules were discovered during 1983–87, 10 new therapeutics during the nineties, and only 5 between 2003 and 2007. Phages are therefore being reconsidered as alternative therapeutics. Phage display technique has proved to be extremely promising for the identification of effective antibodies directed against pathogens, as well as for vaccine development. At the same time, conventional phage therapy uses lytic bacteriophages for treatment of infections and recent clinical trials have shown great potential. Moreover, several other approaches have been developed in vitro and in vivo using phage-derived proteins as antibacterial agents. Finally, their use has also been widely considered for public health surveillance, as biosensor phages can be used to detect food and water contaminations and prevent bacterial epidemics. These novel approaches strongly promote the idea that phages and their proteins can be exploited as an effective weapon in the near future, especially in a world which is on the brink of a “postantibiotic era.”

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Bacteriophages and bacteriophage-derived endolysins as potential therapeutics to combat Gram-positive spore forming bacteria

Cited by 43 publications

References 102 publications

Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis

Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis

Prokaryotic and viral community of the sulfate‐rich crust from Peñahueca ephemeral lake, an astrobiology analogue

Bacteriophages and Their Immunological Applications against Infectious Threats

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