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Updated: Aug 12, 2025
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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
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Genome-wide host-pathogen analyses reveal genetic interaction points in tuberculosis disease
Jody Phelan1, Paula Josefina Gomez-Gonzalez1, Nuria Andreu1
1Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Nature Communications
|February 1, 2023
Summary
Understanding tuberculosis (TB) genetics requires examining host-pathogen interactions. This study reveals specific genetic links between Mycobacterium tuberculosis (Mtb) strains and human immune responses, advancing TB susceptibility research.
Area of Science:
- Genetics
- Immunology
- Microbiology
Background:
- Tuberculosis (TB) pathophysiology genetics remain unclear.
- Human genome-wide association studies (GWAS) have not identified consistent TB susceptibility loci.
- The influence of Mycobacterium tuberculosis (Mtb) genotype on TB outcomes is a significant factor.
Purpose of the Study:
- To investigate genome-genome interactions between human hosts and Mtb.
- To identify specific genetic loci associated with TB susceptibility influenced by Mtb strains.
- To elucidate the co-evolutionary dynamics in TB pathogenesis.
Main Methods:
- Phylogenetic tree-based Mtb-to-human genome-genome analysis.
- Analysis of 714 TB patients from Thailand.
- Identification of genetic interaction points and associated Mtb markers.
Main Results:
- Eight putative genetic interaction points identified (P < 5 × 10⁻⁸).
- Identified human loci DAP and RIMS3 linked to IFNγ and the immune system.
- FSTL5, previously associated with TB susceptibility, was also identified.
- Many associated Mtb markers were lineage-specific.
Conclusions:
- Genome-genome analysis reveals a complex host-pathogen interactome in TB.
- Findings support host-pathogen adaptation and co-evolution in TB.
- Potential for large-scale studies in diverse TB-endemic populations.
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