Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative
Lydia-Eirini Giannakou1, Athanasios-Stefanos Giannopoulos1, Chrissi Hatzoglou1,2
1Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece.
Abstract:
Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.
Insights
Common respiratory bacteria like Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa may contribute to lung adenocarcinoma. They interact with human proteins, affecting cell junctions and apoptosis, potentially driving cancer progression.
Area of Science:
- Microbiology and Molecular Biology
- Genomics and Bioinformatics
- Oncology
Background:
- Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa), and Pseudomonas aeruginosa (Psa) are prevalent gram-negative bacteria causing human respiratory infections.
- Understanding host-pathogen interactions is crucial for elucidating disease mechanisms.
Purpose of the Study:
- To identify human gene interaction networks with Hi, MorCa, and Psa using functional enrichment analysis (FEA).
- To elucidate the spectrum of pathogenicity induced by these common respiratory pathogens.
Main Methods:
- Utilized the Human Pathogen Interaction Database (HPIDB 3.0) to identify interacting human proteins.
- Performed FEA using ToppFun (ToppGene Suite) and GeneCodis to identify enriched Gene Ontologies (GO) for biological processes (BP), cellular components (CC), and diseases.
- Analyzed 11 identified human proteins interacting with the pathogens.
Main Results:
- FEA of BP GOs indicated associations with mitochondrial membrane permeability and apoptotic pathways.
- FEA of CC GOs revealed interactions with focal adhesion, cell junctions, and exosomes.
- The most significant disease and pathway enrichments were lung adenocarcinoma and cell cycle, respectively.
Conclusions:
- Suggests a potential link between Hi, MorCa, and Psa infections and the pathogenesis or progression of lung adenocarcinoma.
- Hypothesizes that these bacteria target epithelial cell junctions, deregulating cell adhesion and apoptosis.
- Recommends experimental validation of these proposed mechanisms.
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