Pilus Phase Variation Switches Gonococcal Adherence to Invasion by Caveolin-1-Dependent Host Cell Signaling

PLoS Pathogens

Michaela Faulstich¹  Martin Fraunholz¹  Thomas Rudel¹  Jan-Peter Böttcher²  Thomas F. Meyer² 

[1] Chair of Microbiology, University of Würzburg Biocenter, Würzburg, Germany;Max Planck Institute for Infection Biology, Dept. Molecular Biology, Berlin, Germany

关键词: Neisseria gonorrhoeae;    Pili;    fimbriae;    Phosphorylation;    Intracellular pathogens;    Antibodies;    CHO cells;    Nystatin;    Phosphates;   

DOI  :  10.1371/journal.ppat.1003373

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Many pathogenic bacteria cause local infections but occasionally invade into the blood stream, often with fatal outcome. Very little is known about the mechanism underlying the switch from local to invasive infection. In the case of Neisseria gonorrhoeae, phase variable type 4 pili (T4P) stabilize local infection by mediating microcolony formation and inducing anti-invasive signals. Outer membrane porin PorBIA, in contrast, is associated with disseminated infection and facilitates the efficient invasion of gonococci into host cells. Here we demonstrate that loss of pili by natural pilus phase variation is a prerequisite for the transition from local to invasive infection. Unexpectedly, both T4P-mediated inhibition of invasion and PorBIA-triggered invasion utilize membrane rafts and signaling pathways that depend on caveolin-1-Y14 phosphorylation (Cav1-pY14). We identified p85 regulatory subunit of PI3 kinase (PI3K) and phospholipase Cγ1 as new, exclusive and essential interaction partners for Cav1-pY14 in the course of PorBIA-induced invasion. Active PI3K induces the uptake of gonococci via a new invasion pathway involving protein kinase D1. Our data describe a novel route of bacterial entry into epithelial cells and offer the first mechanistic insight into the switch from local to invasive gonococcal infection.

【 授权许可】

CC BY