背景:粘附侵袭性大肠杆菌(AIEC)是从克罗恩病(CD)患者中分离出来的。AIEC可以侵入肠上皮,提示其参与CD的发生发展和发病机制。然而,AIEC获得侵袭性表型的机制尚不清楚.
结果:本研究旨在研究AIEC侵袭性的机制。我们发现AIEC中的鞭毛蛋白(fliC)表达比非AIEC菌株高两倍,这种过表达诱导了长丝鞭毛蛋白的形成。在AIECLF82菌株中删除fliC导致鞭毛丝的消失,并减弱了细菌的运动性和侵袭能力,这表明AIEC侵入肠上皮需要通过增加的fliC表达诱导的长丝鞭毛蛋白的形成。在环-di-AMP(c-di-AMP)存在下培养的AIEC和非AIECK12菌株中,FLIC的表达增强,鞭毛丝被拉长。用c-di-AMP刺激增强细菌运动性和侵袭上皮细胞的能力,即使在非AIECK12菌株中。
结论:我们的发现表明,c-di-AMP通过增强fliC的表达在非AIEC菌株上赋予AIEC样表型。该结果将有助于理解CD的发病机制。
BACKGROUND: Adherent-invasive Escherichia coli (AIEC) is isolated from patients with Crohn\'s disease (CD). AIEC can invade the intestinal epithelium, suggesting that it is involved in the development and pathogenesis of CD. However, the mechanism by which AIEC acquired the invasive phenotype remains unknown.
RESULTS: This study was designed to examine the mechanisms of AIEC invasiveness. We found that the flagellin (fliC) expression in AIEC was two-fold higher than that in non-AIEC strains, and this overexpression induced the formation of long-filament flagellin. Deletion of fliC in the AIEC LF82 strain resulted in the disappearance of flagellar filaments and attenuated the motility and invasive ability of the bacterium, suggesting that the formation of long filament flagellin induced by increased fliC expression is required by AIEC to invade the intestinal epithelium. In AIEC and non-AIEC K12 strains cultured in the presence of cyclic-di-AMP (c-di-AMP), the expression of fliC was enhanced, and flagellar filaments were elongated. Stimulation with c-di-AMP enhanced the bacterial motility and ability to invade epithelial cells, even in the non-AIEC K12 strain.
CONCLUSIONS: Our findings show that c-di-AMP confers an AIEC-like phenotype on non-AIEC strains by enhancing the expression of fliC. The results should be useful for understanding the pathogenesis of CD.