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Table 3 Summary of phage therapy studies on C. difficile

From: Emerging applications of phage therapy and fecal virome transplantation for treatment of Clostridioides difficile infection: challenges and perspectives

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]

  1. CDI Clostridioides difficile infection, FFT fecal filtrate transplantation, FVT fecal virome transplantation, PTLPs phage tail-like particles, rCDI recurrent Clostridioides difficile infection, RT ribotype