Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling.
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 l...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3662692?pdf=render |
| _version_ | 1811268723547308032 |
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| author | Michaela Faulstich Jan-Peter Böttcher Thomas F Meyer Martin Fraunholz Thomas Rudel |
| author_facet | Michaela Faulstich Jan-Peter Böttcher Thomas F Meyer Martin Fraunholz Thomas Rudel |
| author_sort | Michaela Faulstich |
| collection | DOAJ |
| description | 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 PorB(IA), 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 PorB(IA)-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. |
| first_indexed | 2024-04-12T21:28:01Z |
| format | Article |
| id | doaj.art-75b1e1ced0804476b05550ece005def2 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-12T21:28:01Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-75b1e1ced0804476b05550ece005def22022-12-22T03:16:07ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0195e100337310.1371/journal.ppat.1003373Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling.Michaela FaulstichJan-Peter BöttcherThomas F MeyerMartin FraunholzThomas RudelMany 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 PorB(IA), 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 PorB(IA)-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.http://europepmc.org/articles/PMC3662692?pdf=render |
| spellingShingle | Michaela Faulstich Jan-Peter Böttcher Thomas F Meyer Martin Fraunholz Thomas Rudel Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling. PLoS Pathogens |
| title | Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling. |
| title_full | Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling. |
| title_fullStr | Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling. |
| title_full_unstemmed | Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling. |
| title_short | Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling. |
| title_sort | pilus phase variation switches gonococcal adherence to invasion by caveolin 1 dependent host cell signaling |
| url | http://europepmc.org/articles/PMC3662692?pdf=render |
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