Manipulation of microvillar proteins during Salmonella enterica invasion results in brush border effacement and actin remodeling

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dc.contributor.authorFelipe-Lopez, Alfonso
dc.contributor.authorHansmeier, Nicole
dc.contributor.authorDanzer, Claudia
dc.contributor.authorHensel, Michael
dc.date.accessioned2023-04-19T21:27:44Z
dc.date.available2023-04-19T21:27:44Z
dc.date.issued2023-03-02
dc.description© 2023 Felipe-Lo´ pez, Hansmeier, Danzer and Hensel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these termsen_US
dc.description.abstractEnterocyte invasion by the gastrointestinal pathogen Salmonella enterica is accompanied by loss of brush border and massive remodeling of the actin cytoskeleton, leading to microvilli effacement and formation of membrane ruffles. These manipulations are mediated by effector proteins translocated by the Salmonella Pathogenicity Island 1-encoded type III secretion system (SPI1- T3SS). To unravel the mechanisms of microvilli effacement and contribution of SPI1-T3SS effector proteins, the dynamics of host-pathogen interactions was analyzed using live cell imaging (LCI) of polarized epithelial cells (PEC) expressing LifeAct-GFP. PEC were infected with S. enterica wild-type and mutant strains with defined defects in SPI1-T3SS effector proteins, and pharmacological inhibition of actin assembly were applied. We identified that microvilli effacement involves two distinct mechanisms: i) F-actin depolymerization mediated by villin and ii), the consumption of cytoplasmic G-actin by formation of membrane ruffles. By analyzing the contribution of individual SPI1-T3SS effector proteins, we demonstrate that SopE dominantly triggers microvilli effacement and formation of membrane ruffles. Furthermore, SopE via Rac1 indirectly manipulates villin, which culminates in F-actin depolymerization. Collectively, these results indicate that SopE has dual functions during F-actin remodeling in PEC. While SopE-Rac1 triggers F-actin polymerization and ruffle formation, activation of PLCg and villin by SopE depolymerizes F-actin in PEC. These results demonstrate the key role of SopE in destruction of the intestinal barrier during intestinal infection by Salmonella.en_US
dc.description.authorstatusFacultyen_US
dc.description.peerreviewyesen_US
dc.description.sponsorshipThis work was supported by the Deutsche Forschungsgemeinschaft grants P4 and Z within the collaborative research center SFB 944. AFL was supported by a research fellowship of the German Academic Exchange Service (DAAD/A-0773175). Mutant strains SB161, SB225, SB856 and M712 were kindly provided by Wolf-Dietrich Hardt, ETH Zürich.en_US
dc.identifier.citationFelipe-Lo´ pez A, Hansmeier N, Danzer C and Hensel M (2023) Manipulation of microvillar proteins during Salmonella enterica invasion results in brush border effacement and actin remodeling. Front. Cell. Infect. Microbiol. 13:1137062. doi: 10.3389/fcimb.2023.1137062en_US
dc.identifier.doi10.3389/fcimb.2023.1137062
dc.identifier.urihttps://hdl.handle.net/10294/15868
dc.language.isoenen_US
dc.publisherFrontiers Mediaen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/us/*
dc.subjecttype III secretion systemen_US
dc.subjectbrush borderen_US
dc.subjectF-actin dynamicsen_US
dc.subjectcell invasionen_US
dc.subjectpolarized epithelial cellen_US
dc.titleManipulation of microvillar proteins during Salmonella enterica invasion results in brush border effacement and actin remodelingen_US
dc.typeArticleen_US
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Nicole Hansmeier