Enterocytes’ tight junctions: From molecules to diseases

Table 5 Interaction between bacterial strains and tight junctional molecules

Vibrio cholerae[87,88]	It expresses zonula occludens toxin that reversibly increases paracellular permeability, triggering phospholipase C and protein kinase Ca dependent actin polymerization
	This process is primary or secondary related to TJ disruption
Shigella flexneri[89]	Secretes heat stable proteins that affect intestinal cells and lead to TJ disruption, even in the absence of living bacteria
Clostridium perfringens[29,31,61,62]	Its enterotoxin interacts with high affinity to claudin-4, therefore also known as CPE-R
	Lower affinity receptors are claudin-3 and occludin. CPE is proposed to be a multifunctional toxin that first induces cell damage at the level of the cell membrane, and thereby relates to TJ proteins, causing structural and functional alterations[61]
	Michl et al[31] have studied the effect of CPE on pancreatic cell cancers that expressed claudin 4[31], and they suggest that targeting of claudin-4 expressing tumors with CPE can represent a promising treatment method
Clostridium difficile[90]	This pathogenic microorganism, known etiologic factor of pseudomembranous colitis, secretes two toxins TcdA and TcdB that act through the Rho GTPase pathway to produce cell damage
	Study for their effect on epithelial TJ structure assumed that they lead to actin rearrangement, actin-ZO1 dissociation and dissociation of TJ components with changes of their cytoplasmic localization[90]
EPEC[91-93]	EPEC secretes through the type III secretion mechanism[87] the EspF protein, that is dose-dependently related to TER and epithelial barrier disruption and cytoplasmic localization of occludin[91]
	These effects seem to relate primary with phosphorylation of 20 kDa myosin light chain and cytoskeletal contraction. Occludin appears dephosphorylated on serine/threonine residues[92]
	The pathogenic action of EPEC on the intestinal epithelium is reversed by Saccharomyces boulardii[93]

CPE: Clostridium perfringens enterotoxin; CPE-R: Clostridium perfringens enterotoxin receptor; EPEC: Enteropathogenic Escherichia coli; TJ: Tight junction; ZO: Zonula occludens; GTPase: Guanosine triphosphatase.