Table 1.
Bacterium | Model | Phage Type | Treatment Outcome | Resistant Found in after Treatment? | Impact of Resistance on Virulence | Receptor | Ref. | |
---|---|---|---|---|---|---|---|---|
Intestinal colonization | Campylobacter jejuni | Chicken intestinal colonization | CP8 and CP34 | Bacterial decrease between 0.5 and 5 log10 CFU/g of caecal contents compared to untreated controls over a 5-day period post-administration. | Yes, at a freq. of 4% | Less infective at low dose. Rapid phenotypic reversion when reintroduced in chicken. | ND | [11,12] |
Campylobacter jejuni | Chicken intestinal colonization | phiCcoIBB35, phiCcoIBB37, and phiCcoIBB12 | Phage cocktail decreases the titre of C. jejuni in faeces by approximately 2 log10 CFU/g when administered orally. | Yes, at a freq. of 13% | Not less infective. No phenotypic reversion when reintroduced in chicken. | ND | [13] | |
Escherichia coli | Calf, piglet, lamb Ta diarrhoea |
B44/1, B44/2, B44/3, P433/1, and P433/2 | Protected calves against a potentially lethal infection, cured diarrhoea in piglets, improved the course of disease in lambs. | Most calves that did not respond to phage treatment had a high number of phage-resistant variants. No phage-resistant mutants were isolated from lambs. | Decreased virulence | Capsular polysaccharides | [14] | |
Escherichia coli | Calf diarrhoea | B41/1 | Rapid reduction of bacterial titres to numbers that are harmless. | Yes | Reduced virulence | Capsular polysaccharides | [15] | |
Escherichia coli | Sheep, mouse, steer intestinal colonization | KH1 and SH1 | Oral phage treatment did not decrease intestinal E. coli in sheep. Decreased the number of E. coli CFU in cattle. Phage therapy cleared the bacteria in a mouse model of intestinal E. coli O157 carriage. | No | - | ND | [16] | |
Escherichia coli | Mouse intestinal colonization | T4 phage, oral | ND | Phage resistant bacterial strains dominated gut after 92 days. | ND | ND | [17] | |
Escherichia coli | Mouse intestinal colonization | cocktail made of phages CLB_P1, CLB_P2, and CLB_P3 | No bacterial level change in the faeces after treatment. | No | - | ND | [18] | |
Enterococcus faecalis | Gnotobiotic mouse intestinal colonization | φ VPE25 | Threefold drop in E. faecalis total intestinal load after 24 h of VPE25 treatment. | Phage resistant variant replaced WT during treatment. | Resistant variants can colonize intestine. | Integral membrane protein PIPEF | [19] | |
Salmonella enterica | Chicken intestinal colonization | cocktail of phages, EP2, MUT3, M4, and YP | Significant difference between phage-treated and untreated groups. | Yes | ND | ND | [20] | |
Salmonella enterica | Chicken intestinal colonization | φ10, φ25, and φ151 | Phages reduced caecal colonization. | Phage-resistance occurred at a frequency commensurate with the titre of phage being administered. | Colonization levels of resistant variants in the ceca did not differ from the controls. Reversion observed after infection. | ND | [21] | |
Vibrio cholerae | Infant mouse and rabbit cholera model | ICP1, ICP2, and ICP3 | Oral administration of phages up to 24 h before V. cholerae challenge reduced colonization of the intestinal tract and prevented cholera-like diarrhoea. | Yes | Variants can colonize intestine. | O-Antigen | [22] | |
Meningitis | Escherichia coli | Mouse meningitis | phage R | One dose of phage was at least equivalent to multiple doses of antibiotics, whether administered intramuscularly or intrathecally. | Yes | Supposably reduced virulence as described in [14]. | Capsular polysaccharides | [23] |
Endocarditis | Pseudomonas aeruginosa | Rat infective endocarditis | cocktail made of phages 12 bacteriophages | 3 log reduction or valve sterilisation when combined with antibiotics. | No | Reduced virulence | LPS and pilus | [24] |
Sepsis | Escherichia coli | Rat neonatal sepsis | phage EC200PP | Phage administered 7 h postinfection rescued 100% of the animals and 50% after 24 h. | Phage resistant variant were found when phage treatment was delayed for 24 h. | Avirulence | ND | [25] |
Klebsiella pneumoniae | Mouse liver abscess and bacteraemia | Phage φNK5 | Intraperitoneal and intragastric administration of phage 30 min after infection protected mice from death in a dose-dependent manner. Decreased bacterial burden and liver damage. | No | Reduced virulence | ND | [26] | |
Staphylococcus aureus | Experimental cow mastitis | Bacteriophage K | Decreased bacterial load after treatment. | Yes | ND | ND | [27] | |
Pseudomonas plecoglossicida | Fish haemorrhagic ascites | PPpW-3 and PPpW-4. Oral | Protective effects of phage treatment with lower and delayed mortality 1 or 24 h after bacterial challenge. | No | Reduced virulence | ND | [28] | |
Klebsiella pneumoniae | Mice acute bacteraemia | GH-K1, GH-K2, and GH-K3 | Phage cocktail significantly enhanced the protection of bacteremic mice against lethal infection. | ND | Reduced virulence | ND | [29] | |
Salmonella enterica Parathyphi B | Mouse sepsis | phage φ1 | Phage given concurrently with a lethal dose of bacteria rescued 100% of the animals. | ND | Avirulence | O-Antigen | [30] | |
pneumonia | Pseudomonas aeruginosa | Mouse acute pneumonia | PAK_P1 | Treatment failed to prevent fatality due to subsequent bacterial outgrowth after 24 h in immunocompromised mice. 100% of bacteria recovered from phage-treated at 24 h were resistant. | Yes, in immunocompromised mice | ND | ND | [31] |
Phage resistant variants for vaccine production and studying virulence factors | Vibrio cholerae | Infant mouse cholera model | ICP1 | ND | ND | Attenuated in vivo. | O-Antigen | [32] |
Vibrio cholerae | Infant mouse cholera model | K139 | ND | ND | Significantly reduced in its ability to colonize the mouse small intestine. | Core oligosaccharide | [33] | |
Vibrio cholerae | Infant mouse cholera model | phage JA1 | ND | ND | Impaired colonization | Capsule/O-antigen | [34] | |
Staphylococcus aureus | Mouse vaccination | MSa phage | ND | ND | Avirulence | Teichoic acids | [35] | |
Yersinia pestis | Mouse vaccination | L-413C, P2 vir1, φ JA1a, φ A1122, T7, T7Ype, Pokrovskaya, Y, PST, Rh | ND | ND | Atenuated or avirulent. | LPS | [36] | |
Flavobacterium columnare | Zebrafish | FCL-1 and FCL-2 | ND | ND | Avirulence | ND | [37] | |
Bacillus thuringiensis | Cecropia moth | φ42, φ51,and φ64 | ND | ND | Decreased virulence | ND | [38] | |
Serratia marcescens | Cecropia moth, Drosophila | Phages φJ and φK | ND | ND | Decreased virulence | ND | [39] | |
Serratia marcescens | Cecropia moth | Phages φJ | ND | ND | Decreased virulence | ND | [40] |