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

• Published in: Infection and immunity Vol. 85; no. 10
• Main Authors: Kido, Junko, Shimohata, Takaaki, Amano, Sachie, Hatayama, Sho, Nguyen, Anh Quoc, Sato, Yuri, Kanda, Yuna, Tentaku, Aya, Fukushima, Shiho, Nakahashi, Mutsumi, Uebanso, Takashi, Mawatari, Kazuaki, Takahashi, Akira
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.10.2017
• Subjects: Bacterial Adhesion; Bacterial Load; Biological Transport; Campylobacter Infections - microbiology; Campylobacter jejuni - pathogenicity; Cellular Microbiology: Pathogen-Host Cell Molecular Interactions; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - physiology; Epithelial Cells - metabolism; Epithelial Cells - microbiology; HEK293 Cells; Humans; Microtubules - physiology; Molecular Motor Proteins - metabolism; Mutation; intracellular bacteria; microtubule; cell invasion; host response to infection; CFTR; Campylobacter jejuni
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.00311-17

is a foodborne pathogen that induces gastroenteritis. Invasion and adhesion are essential in the process of infection leading to gastroenteritis. The mucosal layer plays a key role in the system of defense against efficient invasion and adhesion by bacteria, which is modulated by several ion channels and transporters mediated by water flux in the intestine. The cystic fibrosis transmembrane conductance regulator (CFTR) plays the main role in water flux in the intestine, and it is closely associated with bacterial clearance. We previously reported that infection suppresses CFTR channel activity in intestinal epithelial cells; however, the mechanism and importance of this suppression are unclear. This study sought to elucidate the role of CFTR in infection. Using HEK293 cells that stably express wild-type and mutated CFTR, we found that CFTR attenuated invasion and that it was not involved in bacterial adhesion or intracellular survival but was associated with microtubule-dependent intracellular transport. Moreover, we revealed that CFTR attenuated the function of the microtubule motor protein, which caused inhibition of invasion, but did not affect microtubule stability. Meanwhile, the CFTR mutant G551D-CFTR, which had defects in channel activity, suppressed invasion, whereas the ΔF508-CFTR mutant, which had defects in maturation, did not suppress invasion, suggesting that CFTR suppression of invasion is related to CFTR maturation but not channel activity. When these findings are taken together, it may be seen that mature CFTR inhibits invasion by regulating microtubule-mediated pathways. We suggest that CFTR plays a critical role in cellular defenses against invasion and that suppression of CFTR may be an initial step in promoting cell invasion during infection.