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Evaluation of Potential Therapeutic Targets for Bacterial Infectious Skin Diseases: A Proteome-Wide Mendelian
Zhangren Yan1, Ziyang Shi2, Ye Wang2
1Department of Traditional Chinese Medicine Surgery, Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People's Republic of China.
Background:
Bacterial infectious skin diseases are common dermatological conditions caused by various pathogenic bacteria. In recent years, their incidence has remained high due to factors such as climate change and the overuse of antibiotics, posing persistent challenges for clinical diagnosis and treatment. This study aimed to identify plasma proteins causally associated with cellulitis, erysipelas, cutaneous abscess, furuncle, and carbuncle through Mendelian randomization (MR) analysis.
Methods:
We analyzed genetic instruments of 4907 proteins derived from the Icelandic population together with genome-wide association study (GWAS) data from the FinnGen project to investigate circulating plasma proteins involved in bacterial infectious skin diseases. To validate causal associations, we employed Steiger filtering, reverse MR analysis, phenome-wide association studies (pheWAS), Bayesian colocalization, summary data-based Mendelian randomization (SMR) and (Heterogeneity in Dependent Instruments) HEIDI test. Furthermore, we conducted protein-protein interaction (PPI) network analysis and drug target evaluation to assess therapeutic potential.
Results:
We identified five key proteins associated with bacterial infectious skin diseases. Specifically, FN1 was associated with erysipelas; ULK3 and CSK were associated with cellulitis; and ARHGAP25 and ENTPD6 were associated with cutaneous abscess, furuncle, and carbuncle.
Conclusion:
Through a systematic proteome-wide Mendelian randomization analysis with multiple layers of validation, this study prioritised a set of host plasma proteins associated with different subtypes of bacterial infectious skin diseases, providing a reference for biomarker exploration, further elucidation of disease-related molecular mechanisms, and subsequent research into non-antibiotic intervention strategies.
Insights
This study identified key plasma proteins linked to bacterial skin infections like cellulitis and erysipelas using Mendelian randomization. Findings offer potential biomarkers and non-antibiotic treatment targets for these common dermatological conditions.
Area of Science:
- Genetics
- Dermatology
- Proteomics
Background:
- Bacterial infectious skin diseases are prevalent and challenging to treat.
- Rising incidence linked to climate change and antibiotic resistance.
- Current diagnostic and treatment strategies face persistent challenges.
Purpose of the Study:
- Identify plasma proteins causally associated with specific bacterial skin diseases.
- Utilize Mendelian randomization (MR) for robust causal inference.
- Explore potential biomarkers and therapeutic targets for bacterial skin infections.
Main Methods:
- Proteome-wide Mendelian randomization (MR) analysis on 4907 proteins.
- Integrated Icelandic population data with FinnGen GWAS data.
- Employed multiple validation methods including Steiger filtering, reverse MR, pheWAS, SMR, HEIDI, and PPI network analysis.
Main Results:
- Identified five key plasma proteins associated with bacterial skin diseases.
- FN1 linked to erysipelas.
- ULK3 and CSK associated with cellulitis.
- ARHGAP25 and ENTPD6 linked to cutaneous abscess, furuncle, and carbuncle.
Conclusions:
- Systematic MR analysis prioritized host plasma proteins for bacterial skin disease subtypes.
- Findings provide a reference for biomarker discovery and understanding disease mechanisms.
- Highlights potential for non-antibiotic intervention strategies.
