Change search
ReferencesLink to record
Permanent link

Direct link
Neisseria gonorrhoeae Infection Induces Altered Amphiregulin Processing and Release
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 1, e16369Article in journal (Refereed) Published
Abstract [en]

Adhesion of the human pathogen Neisseria gonorrhoeae has established effects on the host cell and evokes a variety of cellular events including growth factor activation. In the present study we report that infection with N. gonorrhoeae causes altered amphiregulin processing and release in human epithelial cells. Amphiregulin is a well-studied growth factor with functions in various cell processes and is upregulated in different forms cancer and proliferative diseases. The protein is prototypically cleaved on the cell surface in response to external stimuli. We demonstrate that upon infection, a massive upregulation of amphiregulin mRNA is seen. The protein changes its subcellular distribution and is also alternatively cleaved at the plasma membrane, which results in augmented release of an infection-specific 36 kDa amphiregulin product from the surface of human cervical epithelial cells. Further, using antibodies directed against different domains of the protein we could determine the impact of infection on pro-peptide processing. In summary, we present data showing that the infection of N. gonorrhoeae causes an alternative amphiregulin processing, subcellular distribution and release in human epithelial cervical cells that likely contribute to the predisposition cellular abnormalities and anti-apoptotic features of N. gonorrhoeae infections. 

Place, publisher, year, edition, pages
2011. Vol. 6, no 1, e16369
National Category
Biological Sciences Cell and Molecular Biology
Research subject
Microbiology; Molecular Bioscience
URN: urn:nbn:se:su:diva-63651DOI: 10.1371/journal.pone.0016369ISI: 000286663900042OAI: diva2:451606
Available from: 2011-10-26 Created: 2011-10-26 Last updated: 2016-02-05Bibliographically approved
In thesis
1. Host-bacteria interactions: Host cell responses and bacterial pathogenesis
Open this publication in new window or tab >>Host-bacteria interactions: Host cell responses and bacterial pathogenesis
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Helicobacter pylori colonizes the human stomach, where it causes gastritis that may develop into peptic ulcer disease or cancer when left untreated. Neisseria gonorrhoeae colonizes the urogenital tract and causes the sexually transmitted disease gonorrhea. In contrast, Lactobacillus species are part of the human microbiota, which is the resident microbial community, and are considered to be beneficial for health. The first host cell types that bacteria encounter when they enter the body are epithelial cells, which form the border between the inside and the outside, and macrophages, which are immune cells that engulf unwanted material.      

The focus of this thesis has been the interaction between the host and bacteria, aiming to increase our knowledge of the molecular mechanisms that underlie the host responses and their effects on bacterial pathogenicity. Understanding the interactions between bacteria and the host will hopefully enable the development of new strategies for the treatment of infectious disease.

In paper I, we investigated the effect of N. gonorrhoeae on the growth factor amphiregulin in cervical epithelial cells and found that the processing and release of amphiregulin changes upon infection. In paper II, we examined the expression of the transcription factor early growth response-1 (EGR1) in epithelial cells during bacterial colonization. We demonstrated that EGR1 is rapidly upregulated by many different bacteria. This upregulation is independent of the pathogenicity, Gram-staining type and level of adherence of the bacteria, but generally requires viable bacteria and contact with the host cell. The induction of EGR1 is mediated primarily by signaling through EGFR, ERK1/2 and β1-integrins. In paper III, we described the interactions of the uncharacterized protein JHP0290, which is secreted by H. pylori, with host cells. JHP0290 is able to bind to several cell types and induces apoptosis and TNF release in macrophages. For both of these responses, signaling through Src family kinases and ERK is essential. Apoptosis is partially mediated by TNF release. Finally, in paper IV, we showed that certain Lactobacillus strains can reduce the colonization of H. pylori on gastric epithelial cells. Lactobacilli decrease the gene expression of SabA and thereby inhibit the binding mediated by this adhesin.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2016. 42 p.
Host-bacteria interaction, Helicobacter pylori, Neisseria gonorrhoeae, Lactobacillus, Epithelial cells, Macrophages, EGR1, Amphiregulin, SabA
National Category
Research subject
Molecular Bioscience
urn:nbn:se:su:diva-126425 (URN)978-91-7649-331-1 (ISBN)
Public defence
2016-03-18, Vivi Täckholmsalen (Q-salen) NPQ-huset, Svante Arrhenius väg 20, Stockholm, 13:00 (English)

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 4: Manuscript.

Available from: 2016-02-24 Created: 2016-02-01 Last updated: 2016-08-12Bibliographically approved

Open Access in DiVA

Neisseria gonorrhoeae Infection Induces Altered Amphiregulin Processing and Release(1141 kB)87 downloads
File information
File name FULLTEXT01.pdfFile size 1141 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Löfmark, Sonjade Klerk, NeleAro, Helena
By organisation
Department of Genetics, Microbiology and Toxicology
In the same journal
Biological SciencesCell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 87 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 110 hits
ReferencesLink to record
Permanent link

Direct link