Table 1.
List and relevant characteristics of C. difficile phages for which a complete genome sequence is available in GenBank.
| Phage | Family∗ | Genome size (bp) | Accession No. | Date of Release | Relevant characteristics/observations | Reference |
|---|---|---|---|---|---|---|
| phiCD119 | M | 53,325 | AY855346.1 | 2006 | • First C. difficile phage genome to be sequenced • The phage repressor RepR was shown to repress transcription of the five PaLoc genes through binding to the tcdR promoter element |
Govind et al., 2006, 2009 |
| phiC2 | M | 56,538 | DQ466086.1 | 2007 | • Increased TcdB production in certain lysogens carrying phiC2, although transcription of the tcdB gene remained unaffected • Transcription of the tcdA gene was increased or reduced in some lysogens, although the level of TcdA toxin remained unaffected •phiC2 was shown to promote transduction of erythromycin resistance through transfer of the erm(B) gene carried on Tn6215 |
Goh et al., 2005a, 2007, 2013 |
| phiCD27 | M | 50,930 | NC_011398.1 | 2008 | • The phage’s endolysin gene was cloned and expressed in Escherichia coli and Lactococcus lactis. The specificity of the lytic activity of the CD27L endolysin toward C. difficile was demonstrated using a panel of 30 C. difficile isolates + other commensal bacteria • phiCD27 significantly reduced the burden of C. difficile and toxin production in prophylactic assays using in vitro batch fermentation and human colon models |
Mayer et al., 2008; Meader et al., 2010, 2013 |
| phiCD6356 | S | 37,664 | NC_015262.1 | 2010 | • First C. difficile Siphoviridae phage genome to be sequenced | Horgan et al., 2010 |
| phiCD38-2 | S | 41,090 | HM568888.1 | 2011 | • Increased toxin production and PaLoc gene transcription in ribotype 027 lysogens carrying the phiCD38-2 prophage. The impact of phiCD38-2 on toxin production was strain-dependent. • First demonstration of a C. difficile prophage genome maintained as an extrachromosomal plasmid • RNAseq analysis of a R20291-lysogen carrying phiCD38-2 led to the discovery of the antiphage activity of the CwpV phase-variable surface protein |
Sekulovic et al., 2011, 2015 |
| phiMMP02 phiMMP04 |
M M |
48,396 31,674 |
JX145341.1 JX145342.1 |
2012 2012 |
• Free phage particles were isolated from filter-sterilized fecal supernatants from C. difficile infected patients, demonstrating that prophage induction occurs in vivo, during infection | Meessen-Pinard et al., 2012; Boudry et al., 2015 |
| phiCDHM1 | M | 54,279 | NC_024144.1 | 2013 | • The phage genome encodes three homologs of the Staphylococcus aureus Agr quorum sensing (QS) system, namely agrD (pre-peptide of an autoinducing peptide, AIP), agrB (processes the pre-AIP), and agrC (histidine kinase) • Possibly affects QS-mediated phenotypes, although no AgrA-like response regulator could be identified in phiCDHM1 • A cocktail containing phiCDHM1, phiCDHM2, phiCDHM5, and phiCDHM6 was shown to reduce C. difficile burden in vitro and in colonization experiments in hamsters and in a Galleria mellonella larva C. difficile infection model. The phage cocktail also prevented biofilm formation in vitro |
Hargreaves et al., 2014b; Nale et al., 2016a,b |
| phiCDHM13 | M | 33,596 | HG796225.1 | 2013 | Hargreaves et al., 2014a | |
| phiCDHM14 | M | 32,651 | LK985321.1 | 2014 | Hargreaves et al., 2014a | |
| phiCDHM19 | M | 54,295 | LK985322.1 | 2014 | Hargreaves et al., 2014a | |
| phiCD211 phiCDIF1296T |
S S |
131,326 131,326 |
NC_029048.1 CP011970.1 |
2014 2015 |
• phiCD211 and phiCDIF1296T are identical phages • Large phage genome maintained as an extrachromosomal plasmid in lysogens • The genome encodes several genes potentially affecting various phenotypes in C. difficile, including antimicrobial resistance, spore germination, and CRISPR-mediated resistance • Encodes a CRISPR-cas3 gene in addition to a CRISPR array |
Boudry et al., 2015; Wittmann et al., 2015; Garneau et al., 2018 |
| phiCD24-1 | S | 44,129 | LN681534.1 | 2015 | Boudry et al., 2015 | |
| phiCD111 | S | 41,560 | LN681535.1 | 2015 | Sekulovic et al., 2014; Boudry et al., 2015 | |
| phiCD146 | S | 41,507 | LN681536.1 | 2015 | Sekulovic et al., 2014; Boudry et al., 2015 | |
| phiMMP01 phiMMP03 |
M M |
44,461 52,261 |
LN681541.1 LN681542.1 |
2015 2015 |
• Free phage particles were isolated from filter-sterilized fecal supernatants from C. difficile infected patients, demonstrating that prophage induction occurs in vivo, during infection | Meessen-Pinard et al., 2012; Boudry et al., 2015 |
| phiCD481-1 | M | 32,846 | LN681538.1 | 2015 | Sekulovic et al., 2014; Boudry et al., 2015 | |
| phiCD505 | M | 49,316 | LN681539.1 | 2015 | Sekulovic et al., 2014; Boudry et al., 2015 | |
| phiCD506 | M | 33,274 | LN681540.1 | 2015 | Sekulovic et al., 2014; Boudry et al., 2015 | |
| phiCDHM11 | M | 32,000 | HG798901.1 | 2015 | Hargreaves and Clokie, 2015 | |
| phiCDKM9 | M | 49,822 | KX228399 | 2016 | Rashid et al., 2016 | |
| phiCDKM15 | M | 50,605 | KX228400 | 2016 | Rashid et al., 2016 | |
| phiSemix9P1 | N∖ A | 56,606 | KX905163.1 | 2017 | • The phage genome encodes a complete and functional binary toxin locus (CdtLoc) | Riedel et al., 2017 |
∗M, Myoviridae; S, Siphoviridae.