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 | ||
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 | ||
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] |