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Investigation of the invasion mechanism mediated by the outer membrane protein PagN of Salmonella Typhimurium

Abstract : Abstract Background Salmonella can invade host cells via a type three secretion system called T3SS-1 and its outer membrane proteins, PagN and Rck. However, the mechanism of PagN-dependent invasion pathway used by Salmonella enterica , subspecies enterica serovar Typhimurium remains unclear. Results Here, we report that PagN is well conserved and widely distributed among the different species and subspecies of Salmonella . We showed that PagN of S. Typhimurium was sufficient and necessary to enable non-invasive E. coli over-expressing PagN and PagN-coated beads to bind to and invade different non-phagocytic cells. According to the literature, PagN is likely to interact with heparan sulfate proteoglycan (HSPG) as PagN-mediated invasion could be inhibited by heparin treatment in a dose-dependent manner. This report shows that this interaction is not sufficient to allow the internalization mechanism. Investigation of the role of β1 integrin as co-receptor showed that mouse embryo fibroblasts genetically deficient in β1 integrin were less permissive to PagN-mediated internalization. Moreover, PagN-mediated internalization was fully inhibited in glycosylation-deficient pgsA-745 cells treated with anti-β1 integrin antibody, supporting the hypothesis that β1 integrin and HSPG cooperate to induce the PagN-mediated internalization mechanism. In addition, use of specific inhibitors and expression of dominant-negative derivatives demonstrated that tyrosine phosphorylation and class I phosphatidylinositol 3-kinase were crucial to trigger PagN-dependent internalization, as for the Rck internalization mechanism. Finally, scanning electron microscopy with infected cells showed microvillus-like extensions characteristic of Zipper-like structure, engulfing PagN-coated beads and E. coli expressing PagN, as observed during Rck-mediated internalization. Conclusions Our results supply new comprehensions into T3SS-1-independent invasion mechanisms of S. Typhimurium and highly indicate that PagN induces a phosphatidylinositol 3-kinase signaling pathway, leading to a Zipper-like entry mechanism as the Salmonella outer membrane protein Rck.
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Contributor : Nathalie Katy Chanteloup <>
Submitted on : Tuesday, May 25, 2021 - 11:26:11 AM
Last modification on : Friday, June 11, 2021 - 11:46:17 AM


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Emilie Barilleau, Mégane Védrine, Michael Koczerka, Julien Burlaud-Gaillard, Florent Kempf, et al.. Investigation of the invasion mechanism mediated by the outer membrane protein PagN of Salmonella Typhimurium. BMC Microbiology, BioMed Central, 2021, 21 (1), 18 p. ⟨10.1186/s12866-021-02187-1⟩. ⟨hal-03234143⟩



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