FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
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.
Get Full Text
Publication Date: 2016-08-15 PubMed ID: 27342558PubMed Central: PMC4988198DOI: 10.1128/AEM.01166-16Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

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

References

This article includes 42 references
  1. Wada S, Hobo S, Niwa H. Ulcerative keratitis in thoroughbred racehorses in Japan from 1997 to 2008.. Vet Ophthalmol 2010 Mar;13(2):99-105.
    doi: 10.1111/j.1463-5224.2010.00767.xpubmed: 20447028google scholar: lookup
  2. Khosravi AD, Mehdinejad M, Heidari M. Bacteriological findings in patients with ocular infection and antibiotic susceptibility patterns of isolated pathogens.. Singapore Med J 2007 Aug;48(8):741-3.
    pubmed: 17657382
  3. Tümmler B, Wiehlmann L, Klockgether J, Cramer N. Advances in understanding Pseudomonas.. F1000Prime Rep 2014;6:9.
    doi: 10.12703/P6-9pmc: PMC3913036pubmed: 24592321google scholar: lookup
  4. Fleiszig SM, Evans DJ. The pathogenesis of bacterial keratitis: studies with Pseudomonas aeruginosa.. Clin Exp Optom 2002 Sep;85(5):271-8.
    doi: 10.1111/j.1444-0938.2002.tb03082.xpubmed: 12366347google scholar: lookup
  5. Aarestrup FM. Veterinary drug usage and antimicrobial resistance in bacteria of animal origin.. Basic Clin Pharmacol Toxicol 2005 Apr;96(4):271-81.
    doi: 10.1111/j.1742-7843.2005.pto960401.xpubmed: 15755309google scholar: lookup
  6. Balsalobre LC, Dropa M, Matté MH. An overview of antimicrobial resistance and its public health significance.. Braz J Microbiol 2014;45(1):1-5.
    doi: 10.1590/S1517-83822014005000033pmc: PMC4059282pubmed: 24948906google scholar: lookup
  7. Menichetti F, Tagliaferri E. Antimicrobial resistance in internal medicine wards.. Intern Emerg Med 2012 Oct;7 Suppl 3:S271-81.
    doi: 10.1007/s11739-012-0828-3pubmed: 23073868google scholar: lookup
  8. Ishihara K, Saito M, Shimokubo N, Muramatsu Y, Maetani S, Tamura Y. Methicillin-resistant Staphylococcus aureus carriage among veterinary staff and dogs in private veterinary clinics in Hokkaido, Japan.. Microbiol Immunol 2014 Mar;58(3):149-54.
    doi: 10.1111/1348-0421.12128pubmed: 24397564google scholar: lookup
  9. Reardon S. Bacterial arms race revs up.. Nature 2015 May 28;521(7553):402-3.
    doi: 10.1038/521402apubmed: 26017421google scholar: lookup
  10. Fernebro J. Fighting bacterial infections-future treatment options.. Drug Resist Updat 2011 Apr;14(2):125-39.
    doi: 10.1016/j.drup.2011.02.001pubmed: 21367651google scholar: lookup
  11. Abedon ST, Thomas-Abedon C, Thomas A, Mazure H. Bacteriophage prehistory: Is or is not Hankin, 1896, a phage reference?. Bacteriophage 2011 May;1(3):174-178.
    doi: 10.4161/bact.1.3.16591pmc: PMC3225782pubmed: 22164351google scholar: lookup
  12. Hankin E. L'action bactericide des eaux de la Jumna et du Gange sur le vibrion du cholera. Ann Inst Pasteur 1896 10:511.
  13. Dublanchet A, Fruciano E. [A short history of phage therapy].. Med Mal Infect 2008 Aug;38(8):415-20.
    doi: 10.1016/j.medmal.2008.06.016pubmed: 18692974google scholar: lookup
  14. d'Herelle F. Bacteriophage as a Treatment in Acute Medical and Surgical Infections.. Bull N Y Acad Med 1931 May;7(5):329-48.
    pmc: PMC2095997pubmed: 19311785
  15. Ackermann HW. 5500 Phages examined in the electron microscope.. Arch Virol 2007 Feb;152(2):227-43.
    doi: 10.1007/s00705-006-0849-1pubmed: 17051420google scholar: lookup
  16. Johnson RP, Gyles CL, Huff WE, Ojha S, Huff GR, Rath NC, Donoghue AM. Bacteriophages for prophylaxis and therapy in cattle, poultry and pigs.. Anim Health Res Rev 2008 Dec;9(2):201-15.
    doi: 10.1017/S1466252308001576pubmed: 19102791google scholar: lookup
  17. Deresinski S. Bacteriophage therapy: exploiting smaller fleas.. Clin Infect Dis 2009 Apr 15;48(8):1096-101.
    doi: 10.1086/597405pubmed: 19275495google scholar: lookup
  18. Fukuda K, Ishida W, Uchiyama J, Rashel M, Kato S, Morita T, Muraoka A, Sumi T, Matsuzaki S, Daibata M, Fukushima A. Pseudomonas aeruginosa keratitis in mice: effects of topical bacteriophage KPP12 administration.. PLoS One 2012;7(10):e47742.
    doi: 10.1371/journal.pone.0047742pmc: PMC3474789pubmed: 23082205google scholar: lookup
  19. Krylov V, Shaburova O, Krylov S, Pleteneva E. A genetic approach to the development of new therapeutic phages to fight pseudomonas aeruginosa in wound infections.. Viruses 2012 Dec 21;5(1):15-53.
    doi: 10.3390/v5010015pmc: PMC3564109pubmed: 23344559google scholar: lookup
  20. Matsuzaki S, Yasuda M, Nishikawa H, Kuroda M, Ujihara T, Shuin T, Shen Y, Jin Z, Fujimoto S, Nasimuzzaman MD, Wakiguchi H, Sugihara S, Sugiura T, Koda S, Muraoka A, Imai S. Experimental protection of mice against lethal Staphylococcus aureus infection by novel bacteriophage phi MR11.. J Infect Dis 2003 Feb 15;187(4):613-24.
    doi: 10.1086/374001pubmed: 12599078google scholar: lookup
  21. Takemura-Uchiyama I, Uchiyama J, Osanai M, Morimoto N, Asagiri T, Ujihara T, Daibata M, Sugiura T, Matsuzaki S. Experimental phage therapy against lethal lung-derived septicemia caused by Staphylococcus aureus in mice.. Microbes Infect 2014 Jun;16(6):512-7.
    doi: 10.1016/j.micinf.2014.02.011pubmed: 24631574google scholar: lookup
  22. Zimecki M, Artym J, Kocieba M, Weber-Dabrowska B, Borysowski J, Górski A. Effects of prophylactic administration of bacteriophages to immunosuppressed mice infected with Staphylococcus aureus.. BMC Microbiol 2009 Aug 17;9:169.
    doi: 10.1186/1471-2180-9-169pmc: PMC2741470pubmed: 19686585google scholar: lookup
  23. Atterbury RJ. Bacteriophage biocontrol in animals and meat products.. Microb Biotechnol 2009 Nov;2(6):601-12.
    doi: 10.1111/j.1751-7915.2009.00089.xpmc: PMC3815316pubmed: 21255295google scholar: lookup
  24. Soni KA, Nannapaneni R. Removal of Listeria monocytogenes biofilms with bacteriophage P100.. J Food Prot 2010 Aug;73(8):1519-24.
    pubmed: 20819365doi: 10.4315/0362-028x-73.8.1519google scholar: lookup
  25. Nakonieczna A, Cooper CJ, Gryko R. Bacteriophages and bacteriophage-derived endolysins as potential therapeutics to combat Gram-positive spore forming bacteria.. J Appl Microbiol 2015 Sep;119(3):620-31.
    doi: 10.1111/jam.12881pubmed: 26109320google scholar: lookup
  26. Tanji Y, Hattori K, Suzuki K, Miyanaga K. Spontaneous deletion of a 209-kilobase-pair fragment from the Escherichia coli genome occurs with acquisition of resistance to an assortment of infectious phages.. Appl Environ Microbiol 2008 Jul;74(14):4256-63.
    doi: 10.1128/AEM.00243-08pmc: PMC2493164pubmed: 18502917google scholar: lookup
  27. Furusawa T, Iwano H, Higuchi H, Yokota H, Usui M, Iwasaki T, Tamura Y. Bacteriophage can lyse antibiotic-resistant Pseudomonas aeruginosa isolated from canine diseases.. J Vet Med Sci 2016 Jul 1;78(6):1035-8.
    doi: 10.1292/jvms.15-0310pmc: PMC4937139pubmed: 26876365google scholar: lookup
  28. Furusawa T, Iwano H, Higuchi H, Usui M, Maruyama F, Nakagawa I, Yokota H, Tamura Y. Complete Genome Sequences of Broad-Host-Range Pseudomonas aeruginosa Bacteriophages ΦR18 and ΦS12-1.. Genome Announc 2016 May 5;4(3).
    doi: 10.1128/genomeA.00041-16pmc: PMC4859162pubmed: 27151780google scholar: lookup
  29. Synnott AJ, Kuang Y, Kurimoto M, Yamamichi K, Iwano H, Tanji Y. Isolation from sewage influent and characterization of novel Staphylococcus aureus bacteriophages with wide host ranges and potent lytic capabilities.. Appl Environ Microbiol 2009 Jul;75(13):4483-90.
    doi: 10.1128/AEM.02641-08pmc: PMC2704828pubmed: 19411410google scholar: lookup
  30. Wu M, McClellan SA, Barrett RP, Hazlett LD. Beta-defensin-2 promotes resistance against infection with P. aeruginosa.. J Immunol 2009 Feb 1;182(3):1609-16.
    doi: 10.4049/jimmunol.182.3.1609pubmed: 19155510google scholar: lookup
  31. LoPinto AJ, Mohammed HO, Ledbetter EC. Prevalence and risk factors for isolation of methicillin-resistant Staphylococcus in dogs with keratitis.. Vet Ophthalmol 2015 Jul;18(4):297-303.
    doi: 10.1111/vop.12200pubmed: 25130050google scholar: lookup
  32. Schaefer F, Bruttin O, Zografos L, Guex-Crosier Y. Bacterial keratitis: a prospective clinical and microbiological study.. Br J Ophthalmol 2001 Jul;85(7):842-7.
    doi: 10.1136/bjo.85.7.842pmc: PMC1724042pubmed: 11423460google scholar: lookup
  33. Holland SJ, Sanz C, Perham RN. Identification and specificity of pilus adsorption proteins of filamentous bacteriophages infecting Pseudomonas aeruginosa.. Virology 2006 Feb 20;345(2):540-8.
    doi: 10.1016/j.virol.2005.10.020pubmed: 16298408google scholar: lookup
  34. Huff WE, Huff GR, Rath NC, Donoghue AM. Immune interference of bacteriophage efficacy when treating colibacillosis in poultry.. Poult Sci 2010 May;89(5):895-900.
    doi: 10.3382/ps.2009-00528pubmed: 20371840google scholar: lookup
  35. Górski A, Międzybrodzki R, Borysowski J, Dąbrowska K, Wierzbicki P, Ohams M, Korczak-Kowalska G, Olszowska-Zaremba N, Łusiak-Szelachowska M, Kłak M, Jończyk E, Kaniuga E, Gołaś A, Purchla S, Weber-Dąbrowska B, Letkiewicz S, Fortuna W, Szufnarowski K, Pawełczyk Z, Rogóż P, Kłosowska D. Phage as a modulator of immune responses: practical implications for phage therapy.. Adv Virus Res 2012;83:41-71.
    doi: 10.1016/B978-0-12-394438-2.00002-5pubmed: 22748808google scholar: lookup
  36. Owen GR, Brooks AC, James O, Robertson SM. A novel in vivo rabbit model that mimics human dosing to determine the distribution of antibiotics in ocular tissues.. J Ocul Pharmacol Ther 2007 Aug;23(4):335-42.
    doi: 10.1089/jop.2006.0123pubmed: 17803431google scholar: lookup
  37. Marquart ME, O'Callaghan RJ. Infectious keratitis: secreted bacterial proteins that mediate corneal damage.. J Ophthalmol 2013;2013:369094.
    pmc: PMC3556867pubmed: 23365719doi: 10.1155/2013/369094google scholar: lookup
  38. Conibear TCR, Willcox MDP, Flanagan JL, Zhu H. Characterization of protease IV expression in Pseudomonas aeruginosa clinical isolates.. J Med Microbiol 2012 Feb;61(Pt 2):180-190.
    doi: 10.1099/jmm.0.034561-0pubmed: 21921113google scholar: lookup
  39. Tang A, Caballero AR, Marquart ME, O'Callaghan RJ. Pseudomonas aeruginosa small protease (PASP), a keratitis virulence factor.. Invest Ophthalmol Vis Sci 2013 Apr 17;54(4):2821-8.
    doi: 10.1167/iovs.13-11788pmc: PMC3632270pubmed: 23548618google scholar: lookup
  40. Shen EP, Tsay RY, Chia JS, Wu S, Lee JW, Hu FR. The role of type III secretion system and lens material on adhesion of Pseudomonas aeruginosa to contact lenses.. Invest Ophthalmol Vis Sci 2012 Sep 21;53(10):6416-26.
    doi: 10.1167/iovs.11-8184pubmed: 22918630google scholar: lookup
  41. Pastagia M, Schuch R, Fischetti VA, Huang DB. Lysins: the arrival of pathogen-directed anti-infectives.. J Med Microbiol 2013 Oct;62(Pt 10):1506-1516.
    doi: 10.1099/jmm.0.061028-0pubmed: 23813275google scholar: lookup
  42. Yang H, Yu J, Wei H. Engineered bacteriophage lysins as novel anti-infectives.. Front Microbiol 2014;5:542.
    doi: 10.3389/fmicb.2014.00542pmc: PMC4199284pubmed: 25360133google scholar: lookup

Citations

This article has been cited 30 times.
  1. Marasini S, Craig JP, Dean SJ, Leanse LG. Managing Corneal Infections: Out with the old, in with the new?. Antibiotics (Basel) 2023 Aug 18;12(8).
    doi: 10.3390/antibiotics12081334pubmed: 37627753google scholar: lookup
  2. Gao X, Liu J, Li B, Xie J. Antibacterial Activity and Antibacterial Mechanism of Lemon Verbena Essential Oil. Molecules 2023 Mar 30;28(7).
    doi: 10.3390/molecules28073102pubmed: 37049865google scholar: lookup
  3. Fujiki J, Nakamura T, Nakamura K, Nishida K, Amano Y, Watanabe Y, Gondaira S, Usui M, Shimizu M, Miyanaga K, Watanabe S, Iwasaki T, Kiga K, Hanawa T, Higuchi H, Sawa T, Tanji Y, Tamura Y, Cui L, Iwano H. Biological properties of Staphylococcus virus ΦSA012 for phage therapy. Sci Rep 2022 Dec 9;12(1):21297.
    doi: 10.1038/s41598-022-25352-6pubmed: 36494564google scholar: lookup
  4. Xu HM, Xu WM, Zhang L. Current Status of Phage Therapy against Infectious Diseases and Potential Application beyond Infectious Diseases. Int J Clin Pract 2022;2022:4913146.
    doi: 10.1155/2022/4913146pubmed: 36263241google scholar: lookup
  5. Arumugam SN, Manohar P, Sukumaran S, Sadagopan S, Loh B, Leptihn S, Nachimuthu R. Antibacterial efficacy of lytic phages against multidrug-resistant Pseudomonas aeruginosa infections in bacteraemia mice models. BMC Microbiol 2022 Aug 1;22(1):187.
    doi: 10.1186/s12866-022-02603-0pubmed: 35909125google scholar: lookup
  6. Damnjanović D, Vázquez-Campos X, Elliott L, Willcox M, Bridge WJ. Characterisation of Bacteriophage vB_SmaM_Ps15 Infective to Stenotrophomonas maltophilia Clinical Ocular Isolates. Viruses 2022 Mar 29;14(4).
    doi: 10.3390/v14040709pubmed: 35458438google scholar: lookup
  7. Fujiki J, Yoshida SI, Nakamura T, Nakamura K, Amano Y, Nishida K, Nishi K, Sasaki M, Iwasaki T, Sawa H, Komatsuzawa H, Hijioka H, Iwano H. Novel Virulent Bacteriophage ΦSG005, Which Infects Streptococcus gordonii, Forms a Distinct Clade among Streptococcus Viruses. Viruses 2021 Sep 29;13(10).
    doi: 10.3390/v13101964pubmed: 34696394google scholar: lookup
  8. Rahimzadeh G, Saeedi M, Nokhodchi A, Moosazadeh M, Ghasemi M, Rostamkalaei SS, Mortazavi P, Eghbali M, Pourbakhshian R, Rezai MS, Nemati Hevelaee E. Evaluation of in-situ gel-forming eye drop containing bacteriophage against Pseudomonas aeruginosa keratoconjunctivitis in vivo. Bioimpacts 2021;11(4):281-287.
    doi: 10.34172/bi.2021.10pubmed: 34631490google scholar: lookup
  9. Ferriol-González C, Domingo-Calap P. Phage Therapy in Livestock and Companion Animals. Antibiotics (Basel) 2021 May 11;10(5).
    doi: 10.3390/antibiotics10050559pubmed: 34064754google scholar: lookup
  10. Penziner S, Schooley RT, Pride DT. Animal Models of Phage Therapy. Front Microbiol 2021;12:631794.
    doi: 10.3389/fmicb.2021.631794pubmed: 33584632google scholar: lookup
  11. Cieślik M, Bagińska N, Górski A, Jończyk-Matysiak E. Animal Models in the Evaluation of the Effectiveness of Phage Therapy for Infections Caused by Gram-Negative Bacteria from the ESKAPE Group and the Reliability of Its Use in Humans. Microorganisms 2021 Jan 20;9(2).
    doi: 10.3390/microorganisms9020206pubmed: 33498243google scholar: lookup
  12. Nakamura T, Kitana J, Fujiki J, Takase M, Iyori K, Simoike K, Iwano H. Lytic Activity of Polyvalent Staphylococcal Bacteriophage PhiSA012 and Its Endolysin Lys-PhiSA012 Against Antibiotic-Resistant Staphylococcal Clinical Isolates From Canine Skin Infection Sites. Front Med (Lausanne) 2020;7:234.
    doi: 10.3389/fmed.2020.00234pubmed: 32587860google scholar: lookup
  13. Wang JL, Kuo CF, Yeh CM, Chen JR, Cheng MF, Hung CH. Efficacy of φkm18p phage therapy in a murine model of extensively drug-resistant Acinetobacter baumannii infection. Infect Drug Resist 2018;11:2301-2310.
    doi: 10.2147/IDR.S179701pubmed: 30532563google scholar: lookup
  14. Fujiki J, Nakamura T, Furusawa T, Ohno H, Takahashi H, Kitana J, Usui M, Higuchi H, Tanji Y, Tamura Y, Iwano H. Characterization of the Lytic Capability of a LysK-Like Endolysin, Lys-phiSA012, Derived from a Polyvalent Staphylococcus aureus Bacteriophage. Pharmaceuticals (Basel) 2018 Feb 24;11(1).
    doi: 10.3390/ph11010025pubmed: 29495305google scholar: lookup
  15. Hilbert M, Csadek I, Auer U, Hilbert F. Antimicrobial Resistance-Transducing Bacteriophages Isolated from Surfaces of Equine Surgery Clinics - A Pilot Study. Eur J Microbiol Immunol (Bp) 2017 Dec 18;7(4):296-302.
    doi: 10.1556/1886.2017.00032pubmed: 29403658google scholar: lookup
  16. Iwano H, Inoue Y, Takasago T, Kobayashi H, Furusawa T, Taniguchi K, Fujiki J, Yokota H, Usui M, Tanji Y, Hagiwara K, Higuchi H, Tamura Y. Bacteriophage ΦSA012 Has a Broad Host Range against Staphylococcus aureus and Effective Lytic Capacity in a Mouse Mastitis Model. Biology (Basel) 2018 Jan 9;7(1).
    doi: 10.3390/biology7010008pubmed: 29315249google scholar: lookup
  17. Latz S, Krüttgen A, Häfner H, Buhl EM, Ritter K, Horz HP. Differential Effect of Newly Isolated Phages Belonging to PB1-Like, phiKZ-Like and LUZ24-Like Viruses against Multi-Drug Resistant Pseudomonas aeruginosa under Varying Growth Conditions. Viruses 2017 Oct 27;9(11).
    doi: 10.3390/v9110315pubmed: 29077053google scholar: lookup
  18. Shatzkes K, Singleton E, Tang C, Zuena M, Shukla S, Gupta S, Dharani S, Onyile O, Rinaggio J, Connell ND, Kadouri DE. Predatory Bacteria Attenuate Klebsiella pneumoniae Burden in Rat Lungs. mBio 2016 Nov 8;7(6).
    doi: 10.1128/mBio.01847-16pubmed: 27834203google scholar: lookup
  19. Abbas M, Abbas G, Fatima, Hashmi AH, Jaffery S, Li Y, Zhao G, Xihe L. Sustainable AGP alternatives: a systems approach to non-antibiotic growth regulators standardization, synergistic formulation and environmental safety. Front Vet Sci 2025;12:1695160.
    doi: 10.3389/fvets.2025.1695160pubmed: 41695212google scholar: lookup
  20. Osei Duah Junior I, Ampong J, Danquah CA. Mechanisms and Evolution of Antimicrobial Resistance in Ophthalmology: Surveillance, Clinical Implications, and Future Therapies. Antibiotics (Basel) 2025 Nov 20;14(11).
    doi: 10.3390/antibiotics14111167pubmed: 41301664google scholar: lookup
  21. Köhne M, Hüsch R, Peh E, Hirnet J, Tönissen A, Müsken M, Plötz M, Kittler S, Sieme H. Newly isolated bacteriophages show efficacy and phage-antibiotic synergy in vitro against the equine genital pathogens Klebsiella pneumoniae and Pseudomonas aeruginosa. BMC Vet Res 2025 Oct 3;21(1):568.
    doi: 10.1186/s12917-025-04989-1pubmed: 41044673google scholar: lookup
  22. Ibrahim R, Kumar P, Aranjani JM. Microbial keratitis in the age of resistance: unlocking the therapeutic potential of phage therapy. Graefes Arch Clin Exp Ophthalmol 2025 Dec;263(12):3287-3299.
    doi: 10.1007/s00417-025-06961-zpubmed: 40965568google scholar: lookup
  23. Fujiki J, Yokoyama D, Yamamoto H, Kimura N, Shimizu M, Kobayashi H, Nakamura K, Iwano H. Biocontrol of Phage Resistance in Pseudomonas Infections: Insights into Directed Breaking of Spontaneous Evolutionary Selection in Phage Therapy. Viruses 2025 Aug 4;17(8).
    doi: 10.3390/v17081080pubmed: 40872794google scholar: lookup
  24. Urgeya KD, Subedi D, Kumar N, Willcox M. The Ability of Bacteriophages to Reduce Biofilms Produced by Pseudomonas aeruginosa Isolated from Corneal Infections. Antibiotics (Basel) 2025 Jun 20;14(7).
    doi: 10.3390/antibiotics14070629pubmed: 40723932google scholar: lookup
  25. Köhne M, Hüsch R, Tönissen A, Schmidt M, Müsken M, Böttcher D, Hirnet J, Plötz M, Kittler S, Sieme H. Isolation and characterization of bacteriophages specific to Streptococcus equi subspecies zooepidemicus and evaluation of efficacy ex vivo. Front Microbiol 2024;15:1448958.
    doi: 10.3389/fmicb.2024.1448958pubmed: 39529671google scholar: lookup
  26. Junya O, Jumpei F, Kinoshita M, Sudo K, Kawaguchi K, Inoue K, Naito Y, Moriyama K, Nakamura T, Iwano H, Sawa T. Effects of the combination of anti-PcrV antibody and bacteriophage therapy in a mouse model of Pseudomonas aeruginosa pneumonia. Microbiol Spectr 2024 Oct 23;12(12):e0178124.
    doi: 10.1128/spectrum.01781-24pubmed: 39440986google scholar: lookup
  27. Alipour-Khezri E, Skurnik M, Zarrini G. Pseudomonas aeruginosa Bacteriophages and Their Clinical Applications. Viruses 2024 Jun 29;16(7).
    doi: 10.3390/v16071051pubmed: 39066214google scholar: lookup
  28. Fujiki J, Nakamura K, Ishiguro Y, Iwano H. Using phage to drive selections toward restoring antibiotic sensitivity in Pseudomonas aeruginosa via chromosomal deletions. Front Microbiol 2024;15:1401234.
    doi: 10.3389/fmicb.2024.1401234pubmed: 38812675google scholar: lookup
  29. Karn SL, Gangwar M, Kumar R, Bhartiya SK, Nath G. Phage therapy: a revolutionary shift in the management of bacterial infections, pioneering new horizons in clinical practice, and reimagining the arsenal against microbial pathogens. Front Med (Lausanne) 2023;10:1209782.
    doi: 10.3389/fmed.2023.1209782pubmed: 37928478google scholar: lookup
  30. Marshall K, Marsella R. Topical Bacteriophage Therapy for Staphylococcal Superficial Pyoderma in Horses: A Double-Blind, Placebo-Controlled Pilot Study. Pathogens 2023 Jun 14;12(6).
    doi: 10.3390/pathogens12060828pubmed: 37375518google scholar: lookup
Subscribe to our newsletter
Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.