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Applied and environmental microbiology2016; 82(17); 5332-5339; doi: 10.1128/AEM.01166-16

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

Abstract: 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 ΦR18 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. Antibiotic-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.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Publication Date: 2016-08-15 PubMed ID: 27342558PubMed Central: PMC4988198DOI: 10.1128/AEM.01166-16Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explores the potential of using bacteriophages (viruses that infect bacteria) as an alternative treatment for bacterial equine keratitis, a condition in horses primarily caused by certain bacteria which can lead to rapid corneal damage and even blindness. Initial experiments in a mouse model have shown promising results, potentially pointing towards this method as an effective future treatment to manage the condition.

Background

  • The research is based on the problem of bacterial keratitis in horses, which is often caused by staphylococci, streptococci, and pseudomonads.
  • Of these bacteria, Pseudomonas aeruginosa is known to cause rapid corneal damage and in some instances, blindness.
  • Current treatments are impacted by rising antimicrobial resistance, necessitating the need for alternative treatment strategies.

Research Methodology

  • The researchers explored the potential use of bacteriophages, viruses that specifically infect and kill bacteria, to treat horse bacterial keratitis.
  • Phages from the Myoviridae and Podoviridae families, known for their broad host range, were isolated as potential treatment agents.
  • The selected phages were found to adsorb efficiently to host bacteria, with over 80% of a particular phage type (ΦR18) adsorbed to host cells within 30 seconds.

Results

  • The experiments were conducted on a keratitis mouse model, and results demonstrated that administering phage treatment within three hours could effectively kill bacteria and suppress keratitis.
  • A certain ratio (multiplicity of infection) of 100 times the host bacterial number was found effective in killing host bacteria.
  • A cocktail of two phages showed potential in suppressing bacteria in the keratitis mouse model.
  • The phages in the study could completely prevent keratitis caused by P. aeruginosa in the experiment.

Conclusion

  • The results are indicative of the potential that phage treatment has to be a more effective prophylaxis for horse keratitis than current antibiotic treatment options.
  • The researchers recommend further studies to completely assess the potential of phage therapy as treatment for horse keratitis.
  • This suggests that exploring phage therapy will not only provide an alternative treatment method, but also aid in reducing antibiotic usage, and therefore curb the spread of antibiotic resistance.

Cite This Article

APA
Furusawa T, Iwano H, Hiyashimizu Y, Matsubara K, Higuchi H, Nagahata H, Niwa H, Katayama Y, Kinoshita Y, Hagiwara K, Iwasaki T, Tanji Y, Yokota H, Tamura Y. (2016). Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis. Appl Environ Microbiol, 82(17), 5332-5339. https://doi.org/10.1128/AEM.01166-16

Publication

Applied and environmental microbiology
ISSN: 1098-5336
NlmUniqueID: 7605801
Country: United States
Language: English
Volume: 82
Issue: 17
Pages: 5332-5339

Researcher Affiliations

Furusawa, Takaaki
  • Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
Iwano, Hidetomo
  • Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan h-iwano@rakuno.ac.jp.
Hiyashimizu, Yutaro
  • Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
Matsubara, Kazuki
  • Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
Higuchi, Hidetoshi
  • Laboratory of Veterinary Hygiene, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
Nagahata, Hajime
  • Laboratory of Veterinary Hygiene, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
Niwa, Hidekazu
  • Microbiology Division, Tochigi Branch, Epizootic Research Center, Equine Research Institute, Japan Racing Association, Tochigi, Japan.
Katayama, Yoshinari
  • Microbiology Division, Tochigi Branch, Epizootic Research Center, Equine Research Institute, Japan Racing Association, Tochigi, Japan.
Kinoshita, Yuta
  • Microbiology Division, Tochigi Branch, Epizootic Research Center, Equine Research Institute, Japan Racing Association, Tochigi, Japan.
Hagiwara, Katsuro
  • Laboratory of Veterinary Virology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
Iwasaki, Tomohito
  • Laboratory of Applied Biochemistry, School of Food Science and Human Wellness, Rakuno Gakuen University, Ebetsu, Japan.
Tanji, Yasunori
  • Department of Bioengineering, Tokyo Institute of Technology, Yokohama, Japan.
Yokota, Hiroshi
  • Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
Tamura, Yutaka
  • Laboratory of Food Microbiology and Food Safety, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.

MeSH Terms

  • Animals
  • Bacteriophages / physiology
  • Horse Diseases / microbiology
  • Horse Diseases / therapy
  • Horses
  • Keratitis / microbiology
  • Keratitis / therapy
  • Keratitis / veterinary
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myoviridae / physiology
  • Phage Therapy
  • Podoviridae / physiology
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / therapy
  • Pseudomonas Infections / veterinary
  • Pseudomonas aeruginosa / physiology
  • Pseudomonas aeruginosa / virology

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