Toxin A (tcdA) |
Inactivate Rho GTPases. Disrupts the cytoskeleton resulting in disruption of tight junctions and loss of intestinal barrier function. |
(Barth et al., 2001; Egerer et al., 2009; Gerhard et al., n.d.; Jank et al., 2007; Just et al., 1995; Madan and Petri, 2012; Oezguen et al., 2012; Papatheodorou et al., 2010; Qa’Dan et al., 2000) |
Toxin B (tcdB) |
Inactivate Rho GTPases. Disrupts the cytoskeleton resulting in disruption of tight junctions and loss of intestinal barrier function. Huge diversity of subtypes, undergoes accelerated evolution. |
(Barth et al., 2001; Egerer et al., 2009; Gerhard et al., n.d.; Jank et al., 2007; Just et al., 1995; Madan and Petri, 2012; Oezguen et al., 2012; Papatheodorou et al., 2010; Qa’Dan et al., 2000; Shen et al., 2020) |
C. difficile binary toxin (CDT) |
ADP-ribosyltransferase which causes depolymerisation of the actin cytoskeleton (leading to loss of barrier function and disruption of tight junctions) and microtubule protrusions (leading to increased C. difficile adherence). |
(Aktories et al., 2011; Gerding et al., 2014; Hemmasi et al., 2015; Papatheodorou et al., 2010; Schwan et al., 2009) |
SlpA |
Major S-layer constituent. S-layer null strain avirulent in hamster model, and more susceptible to lysozyme and immune effectors. Mutants making more porous S-layer display increased lysozyme sensitivity. |
(Calabi et al., 2002; Kirk et al., 2017; Lanzoni-Mangutchi et al., 2022; Merrigan et al., 2013) |
Cwp2 |
Implicated in adhesion. Dominant antigen in patient sera. |
(Bradshaw et al., 2017) |
Cwp84 |
Required for normal S-layer production. Dominant antigen in patient sera. However, mutants fully virulent in hamster models. |
(Wright et al., n.d.; Kirby et al., 2009) |
Cwp66 |
Implicated in adhesion and stress tolerance. |
(Waligora et al., 2001; Zhou et al., 2022) |
Cwp19 |
Transglycosylase involved in autolysis, resulting in toxin release. |
(Wydau-Dematteis et al., 2018) |
Cwp22 |
Peptidoglycan cross-linking enzyme (L,D-transpeptidase). Supports cell wall integrity. Mutation reduced toxin production, increased cell permeability and autolysis, and reduced adherence. |
(Peltier et al., 2011; Zhu et al., 2019) |
CwpV |
Large phase-variable CWP. Displays auto-aggregative properties. Putatively involved in colonisation and biofilm in vivo. Confers resistance to some bacteriophage. |
(Lawley et al., 2009; Reynolds et al., 2011; Sekulovic et al., 2015) |
CD2831 |
Collagen binding protein involved in adhesion, biofilm formation and immune evasion. |
(Arato et al., 2019) |
CpbA |
Involved in adherence through enhancing collagen interaction and extracellular matrix adherence. |
(Tulli et al., 2013) |
Broader virulence traits |
Lysozyme resistance |
Resistance to hydrolysis via lysozyme due to σV activation of PgdA and PdaV. S-layer provides barrier protection. Required for successful pathogenesis in hamster models. |
(Callewaert and Michiels, 2010; Fagan et al., 2009; Ho et al., 2014; Kaus et al., 2020; Lanzoni-Mangutchi et al., 2022) |
Biofilm |
Contributes to antimicrobial resistance, resistance to oxygen stress, persistence and recurrence of CDI. |
(Bordeleau et al., 2014; Ðapa et al., 2012; Dawson et al., 2012; Frost et al., 2021; Poquet et al., 2018; Semenyuk et al., 2015; Soavelomandroso et al., 2017) |
Spore formation |
Essential for transmission of C. difficile and resistance to environmental stressors, such as oxygen, heat and UV damage. Enables disease persistence. Increased sporulation efficiency possibly increases disease transmission. |
(Burns et al., 2011; Donnelly et al., 2016; Fimlaid et al., 2013; Merrigan et al., 2013; Nerber and Sorg, 2021; Setlow, 2007, 2006) |
tcdC truncation |
Truncation thought to increase production of toxins A and B, associated with hypervirulence in ribotype 027 strains. |
(Carter et al., 2011; Gerding et al., 2014; Warny et al., 2005) |