Virulence factor-dependent basolateral invasion of choroid plexus epithelial cells by pathogenic Escherichia coli in vitro

Abstract

Escherichia coli is the most common Gram-negative causative agent of neonatal meningitis and E. coli meningitis is associated with high morbidity and mortality. Previous research has been carried out with regard to the blood-brain barrier and thereby unveiled an assortment of virulence factors involved in E. coli meningitis. Little, however, is known about the role of the blood-cerebrospinal fluid (CSF) barrier (BCSFB), in spite of several studies suggesting that the choroid plexus (CP) is a possible entry point for E. coli into the CSF spaces. Here, we used a human CP papilloma (HIBCPP) cell line that was previously established as valid model for the study of the BCSFB. We show that E. coli invades HIBCPP cells in a polar fashion preferentially from the physiologically relevant basolateral side. Moreover, we demonstrate that deletion of outer membrane protein A, ibeA or neuDB genes results in decreased cell infection, while absence of fimH enhances invasion, although causing reduced adhesion to the apical side of HIBCPP cells. Our findings suggest that the BCSFB might constitute an entry point for E. coli into the central nervous system, and HIBCPP cells are a valuable tool for investigating E. coli entry of the BCSFB.