🧬 Novel Drug Target Identification in Multidrug-Resistant Helicobacter pylori Using Subtractive Genomics
This repository presents a research project aimed at identifying novel drug targets in multidrug-resistant Helicobacter pylori using in silico subtractive genomics approaches. The findings contribute to combatting rising antimicrobial resistance by proposing specific, essential, and non-host homologous targets for future drug development.
Title: Novel Drug Target Identification in Antimicrobial-Resistant Helicobacter pylori Using Subtractive Genomics
Author: Dhanyashri A/P Guruparan
Institution: Management & Science University (MSU), Malaysia
Degree: Bachelor of Bioinformatics (Hons)
Year: 2024
Project Type: Research Project
Keywords: Helicobacter pylori, drug-target, subtractive-genomics, antimicrobial-resistance, PBIT, PSORTb, KEGG, in-silico
Helicobacter pylori is a Gram-negative, spiral bacterium infecting over half the global population. It is linked to conditions like gastritis, ulcers, and gastric cancer. With increasing antibiotic resistance, identifying novel, safe, and specific drug targets is a priority.
This study applied a genome-wide subtractive genomics approach to analyze the H. pylori proteome, filter out human homologs, assess essentiality, virulence, druggability, and subcellular localization, and identify 14 non-homologous, essential, cytoplasmic proteins as viable drug targets.
- Retrieve and curate the complete H. pylori proteome.
- Filter sequences for non-redundancy and functional viability.
- Perform subtractive genomic filtering against:
- Human proteome
- Human anti-targets
- Gut microbiota
- Analyze essentiality, virulence factors, druggability, and localization.
- Identify unique cytoplasmic proteins as novel drug targets.
| Tool/Platform | Purpose |
|---|---|
| NCBI | Genome and protein sequence retrieval |
| CD-HIT | Removal of paralogous/duplicate sequences |
| Galaxy (EU) | Sequence length filtering and preprocessing |
| PBIT | Subtractive genomic analysis pipeline |
| KAAS (KEGG) | Functional annotation and KO filtering against human pathways |
| PSORTb | Subcellular localization prediction for Gram-negative bacteria |
- Sequences retrieved: 1427
- After redundancy filtering: 1294
- After KEGG & subcellular filtering: 14 final cytoplasmic targets
| No. | Protein Name |
|---|---|
| 1 | VirB11 – Type IV secretion system ATPase |
| 2 | Aminodeoxychorismate synthase component II |
| 3 | CrdR – Copper response regulator |
| 4 | Polysaccharide deacetylase |
| 5 | Tryptophan synthase subunit alpha |
| 6 | UDP-4-amino transaminase |
| 7 | NADH-quinone oxidoreductase subunit G |
| 8 | Type II/IV secretion system ATPase subunit |
| 9 | Pyridoxine 5'-phosphate synthase |
| 10 | Bifunctional anthranilate synthase/aminotransferase |
| 11 | Pyridoxal phosphate-dependent aminotransferase |
| 12 | Flagellar biosynthesis protein FlhF |
| 13 | Anthranilate synthase component I |
| 14 | Sensor histidine kinase (HAMP domain) |
These proteins are essential for bacterial survival, cytoplasmic in localization, and non-homologous to humans, minimizing off-target effects.
This study successfully applied subtractive genomics to identify 14 novel, cytoplasmic, non-human homologous drug targets in H. pylori. These proteins represent ideal candidates for narrow-spectrum antibiotics that minimize toxicity and off-target effects in humans. This research lays the groundwork for structure-based drug discovery and future wet-lab validation against multidrug-resistant H. pylori infections.
- Structural modeling and docking of lead inhibitors against identified proteins
- Experimental (wet-lab) validation of cytoplasmic targets
- Exploring these targets in multi-drug synergy and resistance evasion models
- Develop strain-specific antimicrobial therapies based on these targets
This project is licensed under the MIT License. It is freely available for academic and research use only. Attribution to the author and MSU is required in derivative works.
| This work is original and solely belongs to the author (Dhanyashri) and MSU. All materials and results are intended for academic and non-commercial research purposes only.