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A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Signal transduction pathways induced by virulence factors of Neisseria gonorrhoeae
1Max-Planck-Institute for Infection Biology, Department of Molecular Biology, Berlin, Germany.
Abstract:
The obligate human pathogen Neisseria gonorrhoeae infects a variety of human tissues. In recent years, several host cell receptors for the major bacterial adhesins have been identified. While the knowledge of the molecular mechanism of colonisation has helped to understand special aspects of the infection, like the explicit tropism of gonococci for human tissues, the long-term consequences of engaging these receptors are still unknown. A variety of signalling pathways initiated by the activated receptors and by bacterial proteins transferred to the infected cell have been defined which include lipid second messenger, protein kinases, proteases and GTPases. These pathways control important steps of the infection, such as tight adhesion and invasion, the induction of cytokine release, and apoptosis. The detailed knowledge of bacteria-induced signalling pathways could allow the design of new therapeutic approaches which might be advantageous over the classical antibiotics therapy.
Insights
Neisseria gonorrhoeae uses host cell receptors to infect human tissues, triggering signaling pathways that control infection steps. Understanding these pathways could lead to new therapies beyond antibiotics.
Area of Science:
- Microbiology
- Cell Biology
- Infectious Diseases
Background:
- Neisseria gonorrhoeae is an obligate human pathogen infecting various tissues.
- Host cell receptors for bacterial adhesins have been identified, aiding understanding of gonococcal tropism.
- Long-term consequences of receptor engagement and downstream effects remain largely unknown.
Purpose of the Study:
- To investigate the signaling pathways initiated by Neisseria gonorrhoeae receptor engagement.
- To understand how these pathways influence critical infection processes.
- To explore potential therapeutic strategies based on this knowledge.
Main Methods:
- Identification of host cell receptors for Neisseria gonorrhoeae adhesins.
- Analysis of signaling pathways activated by receptor-ligand interactions.
- Investigation of bacterial protein translocation into host cells.
- Functional assays to assess impact on adhesion, invasion, cytokine release, and apoptosis.
Main Results:
- Defined signaling pathways involving lipid second messengers, protein kinases, proteases, and GTPases.
- Demonstrated control of tight adhesion, invasion, cytokine release, and apoptosis by these pathways.
- Established a link between receptor activation and cellular responses during infection.
Conclusions:
- Neisseria gonorrhoeae manipulates host cell signaling for infection progression.
- Detailed knowledge of bacteria-induced signaling offers potential for novel therapeutic interventions.
- Therapeutic strategies targeting these pathways may offer advantages over conventional antibiotics.
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