Cystic Fibrosis Transmembrane Conductance Regulator Reduces Microtubule-Dependent Campylobacter jejuni Invasion

Campylobacter jejuni (C. jejuni) is gastroenteritis inducible food-born pathogen. Invasion and adhesion process are essential for leading gastroenteritis in C. jejuni infection process. As against bacterial strategy for efficacy invasion and adhesion, mucosal layer play a key role in defense systems, which modulated by several ion channels and transporters mediated water flux on the intestine. Cystic fibrosis transmembrane conductance regulator (CFTR) play the main role in waterfulux in intestine, and it closely related with bacterial clearance. We previously reported that C. jejuni infection suppresses CFTR channel activity in intestinal epithelial cells, however the mechanism and importance of this suppression is unclear. This study seeks to elucidate the role of CFTR in C. jejuni-infection. Using HEK293 cells that stably express wild type and mutated CFTR, we found that CFTR attenuated C. jejuni invasion, it was not involved bacterial adhesion or intracellular survival but associated with microtubule-dependent cellular transport. Moreover we revealed that CFTR attenuated function of microtubule motor protein but not microtubule stability, which causes inhibition of C. jejuni-invasion. Meanwhile, the CFTR mutant G551D-CFTR, which has defects in channel activity, suppressed C. jejuni-invasion, whereasΔF508-CFTR, which has defects in maturation, did not suppress, suggesting that CFTR suppression of C. jejuni-invasion is related to CFTR maturation but not channel activity.
Taken together, mature CFTR inhibited C. jejuni invasion by regulating microtubule-mediated pathways. We suggest that CFTR plays a critical role in cellular defenses against C. jejuni-invasion, and CFTR suppression may be an initial step in promoting cellular invasion during C. jejuni-infection.

内容要旨・審査要旨・論文本文の公開
本論文は，著者Junko Kidoの学位論文として提出され，学位審査・授与の対象となっている。

© 2017 American Society for Microbiology