Porphyromonas gingivalis secreted factors drive epithelial-mesenchymal transition (EMT) through gingipains and an H2S-mediated bacterial defense system
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Updated: Mar 25, 2026
Porphyromonas gingivalis as a Model Organism for Assessing Interaction of Anaerobic Bacteria with Host Cells
Published on: December 17, 2015
Michal Kazelnik1, Rana Masri1, Michal Caspi1
1Department of Clinical Microbiology and Immunology, Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Abstract:
Dysbiosis of the gut microbiota is strongly associated with a wide range of pathologies, including various types of cancer. Porphyromonas gingivalis (P. gingivalis), an oral bacterium, is implicated in the development of colorectal cancer (CRC), and although the exact mechanisms by which P. gingivalis contributes to CRC remain unclear, and emerging evidence suggests that various bacterial elements are involved in the bacterium's pathogenic effects. Here, we show that P. gingivalis secreted factors promote CRC neoplasia progression by modulating both the Wnt/β-catenin and the Hippo-YAP signaling pathways. Using specific inhibitors and P. gingivalis mutant strains, our findings demonstrate that cysteine proteases, specifically Lysin-gingipain (Kgp) and Argin-gingipain A (RgpA), as well as hydrogen sulfide (H₂S), strongly induce the expression of epithelial-mesenchymal transition (EMT) markers, leading to cell detachment and increased motility. These findings reveal a novel connection between microbial virulence and defense mechanisms, such as H₂S, and host cell transformation, suggesting a potential role for bacterial secreted factors in driving CRC neoplasia.
Insights
Porphyromonas gingivalis secreted factors promote colorectal cancer (CRC) progression by altering key signaling pathways. Bacterial proteases and hydrogen sulfide (H₂S) drive epithelial-mesenchymal transition (EMT), increasing cancer cell motility.
Area of Science:
- Microbiology
- Oncology
- Molecular Biology
Background:
- Gut microbiota dysbiosis is linked to various pathologies, including cancer.
- Porphyromonas gingivalis (P. gingivalis), an oral bacterium, is associated with colorectal cancer (CRC) development.
- The precise mechanisms of P. gingivalis in CRC pathogenesis are not fully understood.
Purpose of the Study:
- To investigate how P. gingivalis secreted factors influence CRC progression.
- To elucidate the roles of specific bacterial components in modulating host cell signaling pathways relevant to cancer.
Main Methods:
- Utilized specific inhibitors and P. gingivalis mutant strains.
- Analyzed the modulation of Wnt/β-catenin and Hippo-YAP signaling pathways.
- Assessed the expression of epithelial-mesenchymal transition (EMT) markers.
Main Results:
- P. gingivalis secreted factors promote CRC neoplasia by modulating Wnt/β-catenin and Hippo-YAP pathways.
- Cysteine proteases (Kgp, RgpA) and hydrogen sulfide (H₂S) from P. gingivalis induce EMT markers.
- These factors increase cancer cell detachment and motility, contributing to CRC progression.
Conclusions:
- Bacterial secreted factors, including proteases and H₂S, play a significant role in driving CRC progression.
- A novel link exists between microbial virulence factors and host cell transformation.
- Targeting these bacterial elements could offer new therapeutic strategies for CRC.
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