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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-96679
  • 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 weMany 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.show moreshow less

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Metadaten
Author: Thomas Rudel, Michaela Faulstich, Jan-Peter Böttcher, Thomas F. Meyer, Martin Fraunholz
URN:urn:nbn:de:bvb:20-opus-96679
Document Type:Journal article
Faculties:Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):PLoS Pathogens
Year of Completion:2013
Source:In: PLoS Pathogens (2013) 9: 5, doi:10.1371/journal.ppat.1003373
DOI:https://doi.org/10.1371/journal.ppat.1003373
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:antibodies; bacterial pathogens; cell membranes; intracellular pathogens; neisseria gonorrhoeae; phosphates; phosphorylation; pili and fimbriae
Release Date:2014/04/30
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2013
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung