Inferring pathogen-host interactions between Leptospira interrogans and Homo sapiens using network theory

Area of Science:

• Microbiology
• Immunology
• Bioinformatics

Background:

• Leptospirosis is an emerging zoonotic disease with epidemic potential, caused by pathogenic Leptospira species.
• Understanding pathogen-host protein interactions (PHPIs) is crucial for elucidating disease pathogenesis.

Purpose of the Study:

• To construct and analyze inter-species and intra-species protein interaction networks of Leptospira interrogans and humans.
• To identify key PHPIs and conserved proteins involved in Leptospira pathogenesis.
• To explore the potential of bacterial membrane proteins as immunotherapeutic targets.

Main Methods:

• Construction and topological analysis of inter-species and intra-species protein interaction networks.
• Identification of key PHPIs based on sub-cellular localization.
• Comparative analysis of conserved proteins across different Leptospira species.

Main Results:

• Inter-species networks exhibited lower connectivity than intra-species networks, suggesting network perturbation.
• 35 out of 586 PHPIs were identified as key interactions.
• Outer membrane proteins (GpsA, MetXA) and periplasmic proteins (Flab, GlyA) were conserved across pathogenic, intermediate, and saprophytic Leptospira.
• Bacterial membrane proteins involved in PHPIs significantly disrupt host immune and metabolic processes.

Conclusions:

• Perturbed inter-species protein interactions may contribute to Leptospirosis development.
• Conserved bacterial membrane proteins involved in PHPIs are critical for pathogenesis.
• These membrane proteins represent promising candidates for vaccine development and immunotherapies against Leptospirosis.