Table 3.
Summary of phage therapy studies on C. difficile
| Type of phage therapy | Phage name | Experiment | Outcome | References |
|---|---|---|---|---|
| Single-phage therapy | CD140 | Hamster |
• Phage treatment improved hamster survival • Phage treatment could not protect from a second infection |
[133] |
| phiCD27 | In vitro batch fermentation and human colon models |
• Reduction of both vegetative cells, and TcdA and TcdB production from C. difficile • Reduction of toxin production by lysogens • No impact on other gut microbes |
[102, 134] | |
| PTLPs derived from C. difficile RT078 | In vitro | • Reduction of vegetative cells from C. difficile | [135] | |
| phiCDHS1 | In vitro |
• Reduction of C. difficile colonization • Negatively impacts on bacterial pathogenicity, such as downregulation of the regulatory genes involved in metabolism and toxin production |
[74, 100] | |
| CDSH1 | In vitro HT-29 tumorigenic colon cell model |
• Reduction of C. difficile adherence • No cytotoxicity to human cells |
[132] | |
| Phage cocktail therapy | phiCDHM1, phiCDHM2, phiCDHM3, phiCDHM4, phiCDHM5, phiCDHM6, phiCDHS1 | In vitro and in vivo (hamster model) |
• Reduction of vegetative cells from C. difficile • Reduction of C. difficile colonization, sporulation in hamster model |
[74] |
| phiCDHM1, phiCDHM2, phiCDHM5, phiCDHM6 | G. mellonella larvae CDI model |
• Reduction and prevention of the biofilm formation in vitro • Phage cocktails were more effective than single phages in preventing biofilm formation |
[98] | |
| phiCDHM1, phiCDHM2, phiCDHM5, phiCDHM6 | In vitro batch fermentation model |
• Reduction of vegetative cells from C. difficile • No impact on other gut microbes like enterobacteria and lactobacilli • Increase in specific commensals, suggesting that phage therapy may protect from further colonization of C. difficile |
[136] | |
| Endolysin therapy | Endolysin catalytic domain CD27L1–179 | In vitro |
• Modified endolysin demonstrated greater effectiveness than CD27 • No impact on other gut microbes • Endolysin could be modified to kill other pathogenic species |
[137] |
| Recombinant protein of catalytic domain of lysin PlyCD (PlyCD1-174) | Ex vivo treatment, mouse colon model |
• Reduction of C. difficile colonization • Little effect on normal commensal bacteria |
[138] | |
| CD11 and CDG endolysins | In silico and in vitro testing | • Two endolysins were identified from the genomic sequences of C. difficile strains | [139] | |
| Recombinant fusion protein of phiC2 lysin (PlyCD) and human defensin protein HD5 | In vitro and in vivo (mouse model) |
• MIC of fusion protein was lower than each protein alone • Reduction of C. difficile toxin production and sporulation in vivo • Increase in survival rate of mouse model |
[140] | |
| Recombinant protein of CWH lysin and CWH351-656 | In vitro and ex vivo |
• Hydrolyzing the cell wall of C. difficile • Prevention of C. difficile spore outgrowth by CWH351-656 |
[141] | |
| Endolysin CD16/50L from HN16-1 and f HN50 | Homodimer in vivo and in vitro | • Hydrolyzing the cell wall of C. difficile | [142] | |
| Engineered phage therapy | Wild-type phiCD24-2, and engineered phiCD24-2 (carrying CRISPR-Cas3 components) | In vitro and in vivo (mouse model) |
• Phage modification increased the lytic activity • Modified phages showed higher efficacy for reducing vegetative cells and the bacterial load in feces compared to wild-type parental phages |
[143] |
| FVT | Sterile FFT | rCDI patients | • FFT restored normal stool habits and eliminated symptoms of CDI for a minimum period of 6 months | [18] |
| Lyophilized sterile FFT | rCDI patients | • FFT cured 75% of patients and improved the CDI symptoms | [144] |
CDI Clostridioides difficile infection, FFT fecal filtrate transplantation, FVT fecal virome transplantation, PTLPs phage tail-like particles, rCDI recurrent Clostridioides difficile infection, RT ribotype