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Russo, Brian

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Russo

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Russo, Brian

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2015 - 20162

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Author's Publications: search.filters.isAuthorOfPublication.03cff5cd-446a-41d8-93ba-1c3a0407907c

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    Shigella flexneri Regulation of ARF6 Activation during Bacterial Entry via an IpgD-Mediated Positive Feedback Loop
    (American Society of Microbiology, 2015) Garza-Mayers, Anna; Miller, Kelly A.; Russo, Brian; Nagda, Dipal V.; Goldberg, Marcia B.
    ABSTRACT Entry into cells is critical for virulence of the human bacterial pathogens Shigella spp. Shigella spp. induce membrane ruffle formation and macropinocytic uptake, but the events instigating this process are incompletely understood. The host small GTPase ADP-ribosylation factor 6 (ARF6) functions in membrane trafficking at the plasma membrane and activates membrane ruffle formation. We demonstrate that ARF6 is required for efficient Shigella flexneri entry, is activated by S. flexneri dependent on the phosphatase activity of the type III secreted effector IpgD, and depends on cytohesin guanine nucleotide exchange factors (GEFs) for recruitment to entry sites. The cytohesin GEF ARF nucleotide binding site opener (ARNO) is recruited to these sites, also dependent on IpgD phosphatase activity. ARNO recruitment is independent of ARF6, indicating that, in addition to the described recruitment of ARNO by ARF6, ARNO is recruited upstream of ARF6. Our data provide evidence that ARF6, IpgD, phosphoinositide species, and ARNO constitute a previously undescribed positive feedback loop that amplifies ARF6 activation at bacterial entry sites, thereby promoting efficient S. flexneri uptake.
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    Intermediate filaments enable pathogen docking to trigger type 3 effector translocation
    (2016) Russo, Brian; Stamm, Luisa M.; Raaben, Matthijs; Kim, Caleb M.; Kahoud, Emily; Robinson, Lindsey; Bose, Sayantan; Queiroz, Ana L.; Herrera, Bobby Brooke; Baxt, Leigh A.; Mor-Vaknin, Nirit; Fu, Yang; Molina, Gabriel; Markovitz, David M.; Whelan, Sean; Goldberg, Marcia
    Type 3 secretion systems (T3SSs) of bacterial pathogens translocate bacterial effector proteins that mediate disease into the eukaryotic cytosol. Effectors traverse the plasma membrane through a translocon pore formed by T3SS proteins. In a genome-wide selection, we identified the intermediate filament vimentin as required for infection by the T3SS-dependent pathogen Shigella flexneri. We found that vimentin is required for efficient T3SS translocation of effectors by S. flexneri and other pathogens that use T3SS, Salmonella Typhimurium and Yersinia pseudotuberculosis. Vimentin and the intestinal epithelial intermediate filament keratin 18 interact with the C-terminus of the Shigella translocon pore protein IpaC. Vimentin and its interaction with IpaC are dispensable for pore formation, but are required for stable docking of S. flexneri to cells; moreover, stable docking triggers effector secretion. These findings establish that stable docking of the bacterium specifically requires intermediate filaments, is a process distinct from pore formation, and is a prerequisite for effector secretion.