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Apical invasion of intestinal epithelial cells by salmonella typhimurium requires villin to remodel the brush border actin cytoskeleton

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Salmonella invasion of intestinal epithelial cells requires extensive, though transient, actin modifications at the site of bacterial entry. The actin-modifying protein villin is present in the brush border where it participates in the constitution of microvilli and in epithelial restitution after damage through its actin-severing activity. We investigated a possible role for villin in Salmonella invasion. The absence of villin, which is normally located at the bacterial entry site, leads to a decrease in Salmonella invasion. Villin is necessary for early membrane-associated processes and for optimal ruffle assembly by balancing the steady-state level of actin. The severing activity of villin is important for Salmonella invasion in vivo. The bacterial phosphatase SptP tightly regulates villin phosphorylation, while the actin-binding effector SipA protects F-actin and counterbalances villin-severing activity. Thus, villin plays an important role in establishing the balance between actin polymerization and actin severing to facilitate the initial steps of Salmonella entry.

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Funding Information: We thank R. Friedman, C. Mulet and T. Pedron for technical help. We thank T. Marlovits for antibodies, H.D. Hardt and J. Galan for Salmonella strains, and D. Zhou and V. Koronakis for plasmids. We acknowledge France-BioImaging infrastructure supported by the French National Research Agency (ANR-10-INSB-04-01, «Investments for the future»). This work was supported by the ERC (P.S. Advanced Grant HOMEOEPITH, number 232798). P.J.S. is an HHMI senior foreign scholar. The authors declare no conflict of interest. Publisher Copyright: © 2015 Elsevier Inc.

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Parasitology Microbiology Virology

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