A Genetic Approach to the Development of New Therapeutic Phages to Fight Pseudomonas Aeruginosa in Wound Infections

Крылов, В. Н.; Shaburova, O. V.; Krylov, S. V.; Плетенева, Е. А.

doi:10.3390/v5010015

Cited by 54 publications

(31 citation statements)

References 99 publications

(119 reference statements)

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“…Another advantage of using phages over antibiotics is that phages can replicate at the site of infection, thus increasing in numbers at the site of infection [39]. In addition, several recent and well-controlled animal studies have demonstrated the potential of phages in antibacterial therapy [11,22].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model

Yang

Gong

et al. 2015

Research in Microbiology

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Section: Introductionmentioning

confidence: 99%

Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model

Yang

Gong

et al. 2015

Research in Microbiology

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“…Today, we are globally threatened by antibiotic-resistant bacteria, and phage therapy is being reassessed as a new strategy for treatment of infectious disease (13,17). Indeed, researchers have reported the efficacy of phage therapy for experimental bacterial disease (18)(19)(20)(21)(22). 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).…”

mentioning

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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“…Virulent phages replicate in their bacterial hosts and destroy them in the process, but lysogenic phages insert their genomes into their hosts' genomes (8). As it has turned out, both lysogenic and virulent bacteriophages are actively involved in the evolution of bacteria, including pathogens (9). A troubling possibility is that there are virulence genes in some phages and these genes can change the pathogenicity of their host bacteria.…”

mentioning

confidence: 99%

T4-Like Phage Bp7, a Potential Antimicrobial Agent for Controlling Drug-Resistant Escherichia coli in Chickens

Zhang

Liu

et al. 2013

Appl Environ Microbiol

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Chicken-pathogenic Escherichia coli is severely endangering the poultry industry in China and worldwide, and antibiotic therapy is facing an increasing problem of antibiotic resistance. Bacteriophages can kill bacteria with no known activity in human or animal cells, making them an attractive alternative to antibiotics. In this study, we present the characteristics of a novel virulent bacteriophage, Bp7, specifically infecting pathogenic multidrug-resistant E. coli. Phage Bp7 was isolated from chicken feces. Bp7 belongs to the family Myoviridae, possessing an elongated icosahedral head and contractile sheathed tail. It has a 168-kb doublestranded DNA genome. For larger yields, its optimal multiplicity of infection (MOI) to infect E. coli was about 0.001. The latent period was 10 to 15 min, and the burst size was 90 PFU/infected cell. It was stable both at pH 5.0 to 10.0 and at 40°C or 50°C for at least 1 h. Bp7 could infect 46% of pathogenic clinical E. coli strains. Bp7 harbored 791 open reading frames (ORFs) and 263 possible genes. Among the 263 genes, 199 possessed amino acid sequence identities with ORFs of phage T4, 62 had identities with other T4-like phages, and only one lacked any database match. The genome of Bp7 manifested obvious division and rearrangement compared to phages T4, JS98, and IME08. Bp7 is a new member of the "T4-like" genus, family Myoviridae. Its wide host range, strong cell-killing activity, and high stability to pH make it an alternative to antimicrobials for controlling drug-resistant E. coli in chickens. Chicken colibacillosis is one of the main bacterial diseases and severely endangers the poultry industry in China and worldwide. Escherichia coli has been identified as a major pathogen (1). Antibiotics are widely used to control chicken colibacillosis, but it is very common for E. coli to be resistant to antibiotics (2, 3). In recent years, nearly 80% of E. coli isolates from diseased animals have manifested severe resistance to antimicrobial drugs (4, 5), so antibiotic therapy is facing an increasing problem of antibiotic resistance. Bacteriophages are now considered a good alternative to antibiotics (6, 7).However, there are many problems with phage therapy, and not every phage strain is appropriate for such therapy. Based upon their replication methods, phages are classified as either virulent or lysogenic. Virulent phages replicate in their bacterial hosts and destroy them in the process, but lysogenic phages insert their genomes into their hosts' genomes (8). As it has turned out, both lysogenic and virulent bacteriophages are actively involved in the evolution of bacteria, including pathogens (9). A troubling possibility is that there are virulence genes in some phages and these genes can change the pathogenicity of their host bacteria. Lysogenic phages transfer genes that express toxin proteins or pathogenic factors among bacterial species (8, 10). For safety reasons, lysogenic phages are not allowed to be used in phage therapy, and if a phage is permitted to be an alternati...

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A Genetic Approach to the Development of New Therapeutic Phages to Fight Pseudomonas Aeruginosa in Wound Infections

Cited by 54 publications

References 99 publications

Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model

Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model

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

T4-Like Phage Bp7, a Potential Antimicrobial Agent for Controlling Drug-Resistant Escherichia coli in Chickens

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