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Mycobacterium tuberculosis H37Rv Short Linear PDZ-Binding Motif Proteins at the Host-Pathogen Interface
Edgar Sevilla-Reyes1, Jorge Rosas-García1, Luis Horacio Gutiérrez-González1
1Laboratory of Transcriptomics and Molecular Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico.
International Journal of Molecular Sciences
|April 14, 2026
Summary
Short linear motifs (SLiMs) called PDZ-binding motifs (PDZbms) are used by Mycobacterium tuberculosis to interact with host proteins. This study reveals PDZbms in Mtb
Area of Science:
- Microbiology
- Molecular Biology
- Bioinformatics
Background:
- Short linear motifs (SLiMs), including PDZ-binding motifs (PDZbms), are crucial for transient protein-protein interactions.
- While PDZbms are known in viral pathogenesis, their role in bacterial systems, particularly in host-pathogen interactions, is less understood.
- Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that utilizes effector proteins secreted via the type VII secretion system (T7SS) for virulence.
Purpose of the Study:
- To investigate the occurrence and function of PDZbms in Mtb's T7SS effector proteins.
- To determine the potential of these bacterial PDZbms to interact with human PDZ domain-containing proteins.
- To explore the broader role of PDZbms in Mtb's interaction with the human host.
Main Methods:
- Molecular docking and support vector machine-based prediction were employed to identify and analyze PDZbms in Mtb Esx proteins.
- Proteome-wide analysis of Mtb H37Rv was conducted to quantify C-terminal PDZbm prevalence.
- Gene Ontology and Reactome pathway enrichment analyses were performed to understand the functional implications of PDZbms.
Main Results:
- PDZbms were identified in most Mtb T7SS Esx effector proteins, with EsxA and EsxG showing strong predicted interactions with human syntenin-1.
- A significant portion (23.1%) of Mtb proteins (≥50 amino acids) were predicted to possess C-terminal PDZbms.
- Enrichment analyses indicated that Mtb PDZbms are involved in host-pathogen interactions, including immune modulation and membrane localization.
Conclusions:
- Mtb utilizes PDZbm-mediated interactions to engage with host proteins, extending the PDZbm mimicry hypothesis to bacterial pathogenesis.
- This interaction represents a potential immune evasion strategy for Mtb.
- The findings suggest a conserved mechanism of virulence and offer avenues for developing host-directed therapeutics.
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