Pathogens may influence tight junctions in two ways. Several bacteria and viruses lower the transepithelial resistance by decreasing the expression of tight junctional proteins making it easier for pathogens to penetrate the tissues. Rhinovirus downregulates the transepithelial resistance of nasal epithelial cells by lowering the mRNA expression of claudin 1, ZO-1, E-Cadherin and occludin [51] . HIV-1 decreases the transepithelial resistance in enterocytes and genital epithelial cells by disrupting claudins 1, 2, 4, occludin and ZO-1 in tight junctions and lowering mRNA expression of claudins 1, 2, 3, 4, 5, occludin and ZO-1 by cytokine involved mechanisms allowing penetration of bacteria and viruses through the leaky barriers [52] . Rotavirus in known to loosen tight junctions in gut epithelial cells by decreasing expression of claudin 3, occluding and ZO-1 [53] . Yersinia enterocolica causes a redistribution of claudins 3, 4 and 8 in colonic HT29/B6 cells with a lowering of transepithelial resistance and diminution of the protein expression of claudins 2, 3, 8 and 10 and ZO-1 [54] . Aggressive strains of E Coli cause dissociation of claudin 1, ZO-1 and occludin from cell membranes along with a decrease in electrical transmembrane potential [55] . Helicobacter pylori causes disruption of claudin 4 expression in tight junctions and its movement to the cytosol in gastric epithelial cells and lowering of claudin 4 protein levels, an effect which is dependent on IL-1β [56] . On the other hand, claudins may be used as receptors or co-receptors in the invasion of bacteria and viruses to cells and tissues. Claudins 1, 6 and 9 serve as a co-receptors for hepatitis C for invading liver and endothelial cells [57, 58] . Claudin 1 also promotes dengue virus entry to cells [59] . Claudins also serve as receptors for some bacterial toxins. A well known example is Clostridium perfringens enterotoxin (CPE) which binds to claudin 3 and 4 [60] . In experimental studies this has been used to destroy claudin 3 and 4 expressing cancer cells with chemical modifications of the toxin [60] . Interestingly, CPE has also been successfully used to destroy metastatic cells expressing claudin 4 in murine tissue [61] . Unfortunately, claudin 4 is many times downregulated in metastatic tissues such as metastatic breast carcinoma [62] or carcinoma metastasis to the lung [63] . The frequent associations of claudins as means and targets for spread of infections could predict putative polymorphisms in claudin molecules. Indeed, 50 variations have been found in the claudin 1 gene region some of which alter susceptibility to hepatitis C infection [64] .