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Several bacterial proteins mediate host cell adhesion, but filamentous hemagglutinin (FhaB) is a principal adhesin because mutants lacking this protein exhibit profound colonization defects. Here, we show that FhaB carries a C-terminal microtubule-binding domain (FhaB-CT), which is translocated into the host-cell cytoplasm to promote bacterial colonization. Cryogenic electron microscopy of microtubule-bound FhaB-CT shows that the domain binds primarily to \u03b1-tubulin through a network of polar interactions. Live-cell microscopy of infected tracheal explants reveals that FhaB-CT delivery is required for\n                  <jats:italic>Bordetella<\/jats:italic>\n                  to occupy a niche at the base of cilia on airway epithelia. Finally, we demonstrate that the microtubule-binding domain is required for long-term colonization of the mouse nasal cavity by\n                  <jats:italic>B. pertussis<\/jats:italic>\n                  . These observations suggest that the FhaB-CT domain is delivered into motile cilia, where it interacts with axonemal microtubules. We propose that\n                  <jats:italic>Bordetella<\/jats:italic>\n                  initially adhere to the tips of cilia, then deploy multiple FhaB adhesin molecules to migrate to the base of the cilial forest. This mechanism enables\n                  <jats:italic>Bordetella<\/jats:italic>\n                  to resist removal by the mucociliary \u2018escalator\u2019 that clears the respiratory tract of microbes and debris.\n                <\/jats:p>","DOI":"10.1101\/2025.06.17.660209","type":"posted-content","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T23:50:24Z","timestamp":1750204224000},"source":"Crossref","is-referenced-by-count":1,"title":["Bacteria deliver a microtubule-binding protein into mammalian cells to promote colonization"],"prefix":"10.64898","author":[{"given":"Michael S.","family":"Costello","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara; Santa Barbara, 93106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan C.","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology & Biochemistry, University of California, Irvine; 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