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Phagocytosis of bacteria reverses the direction of macrophage galvanotaxis, implicating a bioelectrical mechanism to initiate life-threatening disseminations. The force that drives direction reversal of macrophage galvanotaxis is not understood. One hypothesis is that<jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>can alter the electrical properties of the macrophages by modifying host cell surface glycan composition, which is supported by the fact that cleavage of surface-exposed sialic acids with a bacterial neuraminidase severely impairs macrophage galvanotaxis, as well as phagocytosis. Here, we utilize N-glycan profiling by nanoLC-chip QTOF mass cytometry to characterize the bacterial neuraminidase-associated compositional shift of the macrophage glycocalyx, which revealed a decrease in sialylated and an increase in fucosylated and high mannose structures. The<jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content><jats:italic>nanH<\/jats:italic>gene, encoding a putative neuraminidase, is required for invasion and internalization in a human colonic epithelial cell infection model. To determine whether NanH is required for the<jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>infection-dependent direction reversal, we constructed and characterized a<jats:italic>nanH<\/jats:italic>deletion mutant and found that NanH is partially required for<jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>infection in primary murine macrophages. However, compared to wild type<jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>, infection with the<jats:italic>nanH<\/jats:italic>mutant only marginally reduced the cathode-oriented macrophage galvonotaxis, without canceling direction reversal. Together, these findings strongly suggest that while neuraminidase-mediated N-glycan modification impaired both macrophage phagocytosis and galvanotaxis, yet to be defined mechanisms other than NanH may play a more important role in bioelectrical control of macrophage trafficking, which potentially triggers dissemination.<\/jats:p>","DOI":"10.1128\/iai.00516-21","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T03:19:38Z","timestamp":1634613578000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Surface Glycans Regulate Salmonella Infection-Dependent Directional Switch in Macrophage Galvanotaxis Independent of NanH"],"prefix":"10.1128","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-6659","authenticated-orcid":true,"given":"Y. 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