Localization of Alpha‐Actinin‐4 During Infections by Actin Remodeling Bacteria

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Bacterial pathogens cause disease by subverting the structure and function of their target host cells. Several foodborne agents such as Listeria monocytogenes (L. monocytogenes), Shigella flexneri (S. flexneri), Salmonella enterica serovar Typhimurium (S. Typhimurium) and enteropathogenic Escherichia coli (EPEC) manipulate the host actin cytoskeleton to cause diarrheal (and systemic) infections. During infections, these invasive and adherent pathogens hijack the actin filaments of their host cells and rearrange them into discrete actin‐rich structures that promote bacterial adhesion (via pedestals), invasion (via membrane ruffles and endocytic cups), intracellular motility (via comet/rocket tails) and/or intercellular dissemination (via membrane protrusions and invaginations). We have previously shown that actin‐rich structures generated by L. monocytogenes contain the host actin cross‐linker α‐actinin‐4. Here we set out to examine α‐actinin‐4 during other key steps of the L. monocytogenes infectious cycle as well as characterize the subcellular distribution of α‐actinin‐4 during infections with other model actin‐hijacking bacterial pathogens (S. flexneri, S. Typhimurium and EPEC). Although α‐actinin‐4 is absent at sites of initial L. monocytogenes invasion, we show that it is a new component of the membrane invaginations formed during secondary infections of neighboring host cells. Importantly, we reveal that α‐actinin‐4 also localizes to the major actin‐rich structures generated during cell culture infections with S. flexneri (comet/rocket tails and membrane protrusions), S. Typhimurium (membrane ruffles) and EPEC (pedestals). Taken together, these findings suggest that α‐actinin‐4 is a host factor that is exploited by an assortment of actin‐hijacking bacterial pathogens.
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DOI: 10.1002/ar.24548
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Dhanda, AS, Yang, D, Guttman, JA. Localization of alpha‐actinin‐4 during infections by actin remodeling bacteria. Anat Rec. 2020; 1– 20. https://doi.org/10.1002/ar.24548.
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Localization of Alpha‐Actinin‐4 During Infections by Actin Remodeling Bacteria
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