TABLE 1.
Summary of the most relevant studies with targeted P. aeruginosa phage therapy in animal modelsa
| Phage(s) (taxonomy) | Procedure | Result(s) | Reference |
|---|---|---|---|
| Mouse | |||
| KPP12 (Myoviridae) | Phage at an MOI of 100 was applied in the corneal surface of mice 30 min after infection, and the eyes were examined 1, 3, and 5 days after phage application | The treated mice showed only slight corneal opacities on day 1 which gradually faded by day 5 after treatment; the infected control mice had most of the corneas perforated on day 5 | 67 |
| ØNH-4 (Myoviridae) and ØMR299-2 (Podoviridae) | A phage mix suspension with an MOI of 10 was administered intranasally 2 h after infection | The use of the two phages together was able to reduce P. aeruginosa levels by at least 3 to 4 log units from murine lungs in 6 h | 68 |
| P3_CHA (Myoviridae) | Two doses of phage (MOI of 1 and MOI of 10) were applied intranasally 2 h after the onset of infection in the case of curative treatment or 4 days before infection in the case of preventive treatment | The curative phage treatment allowed over 95% survival of mice, and the preventive treatment resulted in 100% survival in the 16 days of the expt | 31 |
| PA1Ø (Siphoviridae) | Phages were administered via intraperitoneal route in normal mice (MOI of 1, 10, and 100) and neutropenic mice (MOI of 10) | Immunocompetent mice treated with phage achieved 80% to 100% survival rates, and no viable bacteria were found in organ samples after 48 h of the phage treatment; phage treatment was inefficient in neutropenic mice infected with P. aeruginosa PAO1 even though it was able to extend their lives for 12 h | 69 |
| PAK-P1 (Myoviridae) | Phages were applied intranasally 2 h after bacterial infection onset (MOI of 0.1, 1, and 10), with expts performed for up to 12 days, or phages were used as a preventive treatment 24 h before infection (MOI of 10), with expts carried out during 16 days | 100% of the mice treated with an MOI of 10 survived until the end of the expt; in the preventive treatment, 100% of pretreated mice survived until the end of the expt, whereas 100% of untreated mice died within 2 days | 30 |
| MPK1 (Myoviridae) and MPK6 (Podoviridae) | Two different doses of phages (MOI of 1 and 10) were tested by administration through i.m. and i.p. routes after 6 to 12 h postinfection | The survival rate of mice achieved after 48 h of treatment with MK1 phage was up to 80% for i.m. administration or 100% for i.p. administration; the results with phage MK6 were significantly lower (about 20% for i.m. and 70% for i.p.) | 70 |
| Cocktail of 3 phages: ATCC 12175-B1, ATCC 14203-B1, and ATCC 14205-B1 | A phage cocktail containing 1 × 108 PFU of each phage was administered i.m., i.p., or s.c. | A single dose of phage cocktail significantly decreased the mortality of thermally injured P. aeruginosa-infected mice from 6% survival without treatment to 22% to 87% survival with treatment, depending on the route of administration | 29 |
| KPP10 (Myoviridae) | To evaluate the efficacy of phages against gut-derived sepsis, 1 × 1010 PFU was orally administered to each mice 1 day before, 1 day after, or 6 days after P. aeruginosa inoculation | Phage significantly protected mice from mortality, achieving a survival rate of 66.7% for the phage-treated group (1 day after infection) vs 0% for the control group; mice treated with phage also had lower numbers of viable P. aeruginosa cells in their blood, liver, and spleen | 33 |
| Catfish | |||
| MBL (Podoviridae) | A phage suspension (1010 PFU/ml) was applied on the infected skin lesion with a cotton swab | Phage therapy effectively cured the ulcerative lesions in infected fish after 8–10 days of treatment, with a 7-fold reduction of the lesion compared with untreated fish | 28 |
| Wax moth larvae | |||
| 14/1 (Myoviridae); φKZ (Myoviridae); PNM (Podoviridae); PT7 (Myoviridae) | Phages were applied by injection in the abdomen and three treatments were tested: phage φKZ applied alone, all phages applied sequentially, and all phages applied simultaneously in a cocktail | Phage therapy increased the life span of infected wax moth larvae: the avg time to death increased from 12.67 h to 26.67 h, 27.33 h, and 33.33 h, respectively, for larvae treated with φKZ, the multiphage sequence, and the phage cocktail; high phage/bacterium ratios completely cleared otherwise-lethal infections | 66 |
| Dog | |||
| NA | Dogs with chronic otitis were treated with a single dose of a phage cocktail (6 phages), containing 1 × 105 PFU of each phage, by direct application into the external auditory canal | 48 h after treatment, the clinical score and P. aeruginosa counts of all isolates from ears significantly decreased (mean score decrease, 30.1%; mean count decrease, 67%) | 71 |
| NA | A dog with P. aeruginosa chronic bilateral otitis externa was treated with 400 PFU of phage instilled into the right auditory canal | Before phage treatment, the ears were similarly erythematous, with copious discharge; 27 h after treatment, the right ear was dry and did not appear inflamed, while the left ear (not treated) remained unchanged; the left ear was then also treated with phage, which dramatically improved its condition | 72 |
| Drosophila melanogaster | |||
| MPK1 (Myoviridae) and MPK6 (Podoviridae) | The antibacterial efficacy of phages administered by feeding at a concn of 5 × 107 PFU was evaluated in Drosophila melanogaster systemic infection | Both phages significantly delayed the PAO1-induced killing, although MPK1 persisted longer than MPK6 in uninfected D. melanogaster tissue samples | 70 |
a
MOI, multiplicity of infection; NA, information not available; i.m., intramuscular; i.p., intraperitoneal; s.c., subcutaneous.