Intracellular pathogens have developed elaborate mechanisms to exploit the different cellular systems of their unwilling hosts to facilitate their entry, replication, and survival. In particular, a diverse range of bacteria and viruses have evolved unique strategies to harness the power of Arp2/3-mediated actin polymerization to enhance their cell-to-cell spread. In this review, we discuss how studying these pathogens has revolutionized our molecular understanding of Arp2/3-dependent actin assembly and revealed key signaling pathways regulating actin assembly in cells. Future analyses of microbe-host interactions are likely to continue uncovering new mechanisms regulating actin assembly and dynamics, as well as unexpected cellular functions for actin. Further, studies with known and newly emerging pathogens will also undoubtedly continue to enhance our understanding of the role of the actin cytoskeleton during pathogenesis and potentially highlight future therapeutic approaches.
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