Virulence Factors of Clostridioides (Clostridium) difficile Linked to Recurrent Infections

Table 1

Summary of presumptive virulence factors associated with recurrent C. difficile infections.

Factor	Mechanism/function	Risk/association	Source
tcdC and binary toxin	Production of elevated toxin A and B levels in hypervirulent strains	Increased pathogenicity in vivo and in vitro	[37]
agr1 locus (accessory-gene regulator)	Positive regulation of toxin A and toxin B production, independent of tcdC	Regulation of virulence, associated with increased colonization	[38–41]
Biofilm	Survival niche of C. difficile with multispecies communities; Accumulation of toxins and biomass in variant strains regulated by quorum sensing	Long persistence/protection of C. difficile	[36, 42–46]
	Accumulation of spores	Reduced susceptibility to antibiotics	[45, 47]
SlpA (S-layer protein A)	Presence and low molecular weight subunits with sequence variability in hypervirulent strains	Increased adhesion to gut mucosa	[48–52]
Cwp84 (cell wall protein 84)	Cleavage of adhesins, such as SlpA, for the paracrystalline layer assembly	Release and dissemination of C. difficile in the host	[49, 52]
	Degradation of several extracellular matrix proteins (fibronectin, laminin, vitronectin)	Increase adhesion and colonization	[48, 49, 53]
	Production of thicker biofilm in strains with high proteolytic activity associated to Cwp84	Enhanced virulence and host-pathogen adherence; maintenance of CDI	[54, 55]
Flagella	Presence of posttranscriptional modifications in flagellin and flagellar cap proteins	Increased biofilm, adherence, and cell internalization, associated with efficient colonization in vivo	[42, 56, 57] [58]
Spores	Development of structural morphotypes of outermost exosporium layers (thin or thick)	Associated to host-spore interactions, dfferences in affinity to epithelial cells	[12, 45, 59, 60]
	Expression of the sporulating regulator spo0A is associated with high spore production and biofilm formation	Transmission of CDI and maintenance of C. difficile in the host, despite the antibiotic treatment	[42, 45, 59, 61–63]