Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements

Boettcher, Jan Peter; Kirchner, Marieluise; Churin, Y; Kaushansky, Alexis; Pompaiah, Malvika; Thorn, Hans; Brinkmann, Volker; MacBeath, Gavin; Meyer, Thomas F.

doi:10.1371/journal.pbio.1000457

Cited by 34 publications

(45 citation statements)

References 52 publications

(61 reference statements)

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“…Although several studies have shown that N. meningitidis adhesion and invasion into human endothelial cells is dependent on Rho-GTPase signaling, none have directly measured protein levels after infection (40,62). The related pathogen, N. gonorrhoeae, has been shown to increase levels of RhoA-GTP in a type IV pilin-dependent manner, resulting in reduced invasion of ME180 endometrial epithelial cells (63). However, in our model, we did not see any differences in cell migration or in actin dynamics in cells infected with pilin mutants.…”

Section: Discussioncontrasting

confidence: 72%

Disease-Associated Neisseria meningitidis Isolates Inhibit Wound Repair in Respiratory Epithelial Cells in a Type IV Pilus-Independent Manner

Ren

MacKichan

2014

Infect Immun

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c Neisseria meningitidis is the causative agent of meningococcal disease. Onset of meningococcal disease can be extremely rapid and can kill within a matter of hours. However, although a much-feared pathogen, Neisseria meningitidis is frequently found in the nasopharyngeal mucosae of healthy carriers. The bacterial factors that distinguish disease-from carriage-associated meningococci are incompletely understood. Evidence suggesting that disruptions to the nasopharynx may increase the risk of acquiring meningococcal disease led us to evaluate the ability of disease-and carriage-associated meningococcal isolates to inhibit cell migration, using an in vitro assay for wound repair. We found that disease-associated isolates in our collection inhibited wound closure, while carriage-associated isolates were more variable, with many isolates not inhibiting wound repair at all. For isolates selected for further study, we found that actin morphology, such as presence of lamellipodia, correlated with cell migration. We demonstrated that multiple meningococcal virulence factors, including the type IV pili, are dispensable for inhibition of wound repair. Inhibition of wound repair was also shown to be an active process, i.e., requiring live bacteria undergoing active protein synthesis.

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Section: Discussioncontrasting

confidence: 72%

Disease-Associated Neisseria meningitidis Isolates Inhibit Wound Repair in Respiratory Epithelial Cells in a Type IV Pilus-Independent Manner

Ren

MacKichan

2014

Infect Immun

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“…T4P-mediated adherence and retraction lead to the rapid formation beneath the microcolonies of cortical plaques (179,280,303), structures enriched in the cytoskeletal proteins actin and ezrin and in signaling proteins such as caveolin, epidermal growth factor receptor (EGFR), CD44, and ICAM-1 (52). Neisseria causes cytoskeletal rearrangements that block bacterial uptake, a phenotype also caused by E. coli expressing bundle-forming pili (52), and induces membrane ruffling, enveloping adherent microcolonies and protecting them from shear forces (283).…”

Section: Manipulation Of Host Cellsmentioning

confidence: 99%

“…Neisseria causes cytoskeletal rearrangements that block bacterial uptake, a phenotype also caused by E. coli expressing bundle-forming pili (52), and induces membrane ruffling, enveloping adherent microcolonies and protecting them from shear forces (283). Neisseria also alters cell signaling and cytokine production (97,314,383,399) and impairs adherens and tight junction integrity, allowing bacteria to traverse polarized cell layers, including those forming the blood-brain barrier (110,111,248,334).…”

Section: Manipulation Of Host Cellsmentioning

confidence: 99%

Type IV Pilin Proteins: Versatile Molecular Modules

Giltner

Nguyen

Burrows

2012

Microbiol Mol Biol Rev

398

519

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SUMMARYType IV pili (T4P) are multifunctional protein fibers produced on the surfaces of a wide variety of bacteria and archaea. The major subunit of T4P is the type IV pilin, and structurally related proteins are found as components of the type II secretion (T2S) system, where they are called pseudopilins; of DNA uptake/competence systems in both Gram-negative and Gram-positive species; and of flagella, pili, and sugar-binding systems in the archaea. This broad distribution of a single protein family implies both a common evolutionary origin and a highly adaptable functional plan. The type IV pilin is a remarkably versatile architectural module that has been adopted widely for a variety of functions, including motility, attachment to chemically diverse surfaces, electrical conductance, acquisition of DNA, and secretion of a broad range of structurally distinct protein substrates. In this review, we consider recent advances in this research area, from structural revelations to insights into diversity, posttranslational modifications, regulation, and function.

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“…In brief, Cav1 interacts directly with Vav2, a Rho-family GEF, and both Vav2 and its substrate, RhoA, play a major role in the Cav1-mediated prevention of bacterial uptake. 79 …”

Section: Rho Gtpases In Ceacam-mediated Neisseria Entrymentioning

confidence: 99%

Rho GTPases as pathogen targets: Focus on curable sexually transmitted infections

2015

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Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements

Abstract: During the early stages of infection, Neisseria gonorrhoeae triggers a phosphotyrosine-dependent Cav1-Vav2-RhoA signaling cascade that promotes the pathogen's extracellular state.

Cited by 34 publications

References 52 publications

Disease-Associated Neisseria meningitidis Isolates Inhibit Wound Repair in Respiratory Epithelial Cells in a Type IV Pilus-Independent Manner

Disease-Associated Neisseria meningitidis Isolates Inhibit Wound Repair in Respiratory Epithelial Cells in a Type IV Pilus-Independent Manner

Type IV Pilin Proteins: Versatile Molecular Modules

Rho GTPases as pathogen targets: Focus on curable sexually transmitted infections

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