{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:35:59Z","timestamp":1785411359505,"version":"3.56.0"},"reference-count":62,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas"},{"id":[{"id":"https:\/\/ror.org\/017fh2655","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Short linear motifs (SLiMs), such as PDZ-binding motifs (PDZbms), are compact interaction modules that mediate transient, specific protein\u2013protein interactions. While PDZbms are well characterized in viral pathogenesis, subverting host protein functions, their role in bacterial systems requires further study. Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that mainly infects macrophages. The type VII secretion system (T7SS) of Mtb secretes a subset of effector proteins (Esx) involved in virulence. By using molecular docking and support vector machine-based prediction, we analyzed PDZbm occurrence in T7SS Esx effector proteins and their ability to bind human PDZ domain-containing proteins. We identified PDZbms in most of the Esx proteins studied, with EsxA and EsxG showing the best PDZ-dependent interaction with syntenin-1, a host scaffold protein involved in vesicular trafficking and immune signaling. Additional Esx proteins were predicted to engage other host PDZ proteins. Proteome-wide analysis of Mtb H37Rv revealed that 23.1% of expressed proteins with \u226550 amino acids contained a C-terminal PDZbm. Gene Ontology and Reactome pathway enrichment revealed their involvement in processes related to bacterial and bacterial\u2013host interactions, including redox balance, immunomodulation, and membrane localization, at various stages of infection. Our results support the existence of a PDZbm-mediated interface between Mtb and the human host, extending the PDZbm mimicry hypothesis beyond viruses to bacterial systems as an immune evasion strategy. This work may open multiple research lines focused on experimental validation and the development of a comparative PDZbm catalogue to uncover conserved virulence mechanisms that may guide the design of host-directed therapeutics.<\/jats:p>","DOI":"10.3390\/ijms27073153","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:09:18Z","timestamp":1774944558000},"page":"3153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mycobacterium tuberculosis H37Rv Short Linear PDZ-Binding Motif Proteins at the Host\u2013Pathogen Interface"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7047-0222","authenticated-orcid":false,"given":"Edgar","family":"Sevilla-Reyes","sequence":"first","affiliation":[{"name":"Laboratory of Transcriptomics and Molecular Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5130-4655","authenticated-orcid":false,"given":"Jorge","family":"Rosas-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory of Transcriptomics and Molecular Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0708-0448","authenticated-orcid":false,"given":"Luis Horacio","family":"Guti\u00e9rrez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratory of Transcriptomics and Molecular Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-5631","authenticated-orcid":false,"given":"Teresa","family":"Santos-Mendoza","sequence":"additional","affiliation":[{"name":"Laboratory of Transcriptomics and Molecular Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.tibs.2020.03.003","article-title":"Mimicry of Short Linear Motifs by Bacterial Pathogens: A Drugging Opportunity","volume":"45","author":"Gibson","year":"2020","journal-title":"Trends Biochem. 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