The aims of the present study were to investigate meprin mRNA expression in ileal biopsies of CD patients since AIEC Vorinostat bacteria show a tropism for ileal colonization in CD patients and to analyse the role of meprins in the interaction of CD-associated E. coli and intestinal epithelial cells. Experiments performed in vitro with cultured intestinal epithelial cells, ex vivo with human isolated enterocytes from CD patients, or in vivo using transgenic mice expressing the human CEACAM6 receptors showed that type 1 pili play a key role in the ability of AIEC bacteria to adhere to and invade intestinal epithelial cells. We investigated whether the MK-4827 decrease in the abilities of AIEC bacteria to adhere to and invade epithelial intestinal cells observed after pretreatment of bacteria with meprin a or meprin b could be the result of proteolytic degradation of type 1 pili by these proteases. A dose-dependent proteolytic degradation of FimA, the major subunit of type 1 pili, was observed after treatment of AIEC LF82 purified type 1 pili with meprins a and b. Treatment of LF82 purified type 1 pili with 100 mg/ml of meprin a or meprin b induced a strong decrease in the FimA band observed on SDS-PAGE compared to untreated type 1 pili. We also analyzed the proteolytic activity of meprins on type 1 pili present on the surface of whole bacteria. The amount of FimA subunit relative to that of the inner membrane protein Lep was determined by Western blot after treatment of LF82 bacteria with active or heat-inactivated meprin a or b. We observed 58% and 34% decreased amounts of FimA after treatment of the bacteria with active meprins a and b, respectively compared to those of untreated bacteria. In contrast, when bacteria were treated with heat-inactivated meprins the amount of FimA was unchanged. The degradation products of purified AIEC LF82 type 1 pili following meprin treatment were analyzed by mass spectrometry. Treatment of purified LF82 type 1 pili with 100 mg/ml of active meprins a and b, compared to heat inactivated meprins, modified the mass spectrometry profile of type 1 pili. A decrease in the intensity of the base peak of spectrum corresponding to the protonated form of major analyte detected between 16259 and 16267 m/z was observed after treatment with meprins.