Neisseria meningitidis differentially controls host cell motility through PilC1 and PilC2 components of type IV Pili.
Neisseria meningitidis is a strictly human pathogen that has two facets since asymptomatic carriage can unpredictably turn into fulminant forms of infection. Meningococcal pathogenesis relies on the ability of the bacteria to break host epithelial or endothelial cellular barriers. Highly restrictive, yet poorly understood, mechanisms allow meningococcal adhesion to cells of only human origin. Adhesion of encapsulated and virulent meningococci to human cells relies on the expression of bacterial type four pili (T4P) that trigger intense host cell signalling. Among the components of the meningococcal T4P, the concomitantly expressed PilC1 and PilC2 proteins regulate pili exposure at the bacterial surface, and until now, PilC1 was believed to be specifically responsible for T4P-mediated meningococcal adhesion to human cells. Contrary to previous reports, we show that, like PilC1, the meningococcal PilC2 component is capable of mediating adhesion to human ME180 epithelial cells, with cortical plaque formation and F-actin condensation. However, PilC1 and PilC2 promote different effects on infected cells. Cellular tracking analysis revealed that PilC1-expressing meningococci caused a severe reduction in the motility of infected cells, which was not the case when cells were infected with PilC2-expressing strains. The amount of both total and phosphorylated forms of EGFR was dramatically reduced in cells upon PilC1-mediated infection. In contrast, PilC2-mediated infection did not notably affect the EGFR pathway, and these specificities were shared among unrelated meningococcal strains. These results suggest that meningococci have evolved a highly discriminative tool for differential adhesion in specific microenvironments where different cell types are present. Moreover, the fine-tuning of cellular control through the combined action of two concomitantly expressed, but distinctly regulated, T4P-associated variants of the same molecule (i.e. PilC1 and PilC2) brings a new model to light for the analysis of the interplay between pathogenic bacteria and human host cells.
Morand
Philippe C
PC
Department of Molecular Biology, Max-Planck-Institute for Infection Biology, Berlin, Germany. philippe.morand@cch.aphp.fr
Drab
Marek
M
Rajalingam
Krishnaraj
K
Nassif
Xavier
X
Meyer
Thomas F
TF
D001422:Bacterial Adhesion; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D017931:DNA Primers; D066246:ErbB Receptors / Q000378:metabolism; D036781:Fimbriae Proteins / Q000235:genetics / Q000502:physiology*; D010861:Fimbriae, Bacterial / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D009345:Neisseria meningitidis / Q000502:physiology*
D017931:DNA Primers; C079208:pilC protein, Neisseria gonorrhoeae; D036781:Fimbriae Proteins; D066246:ErbB Receptors