Pathogens and polymers: Microbe–host interactions illuminate the cytoskeleton

Abstract

Intracellular pathogens subvert the host cell cytoskeleton to promote their own survival, replication, and dissemination. Study of these microbes has led to many discoveries about host cell biology, including the identification of cytoskeletal proteins, regulatory pathways, and mechanisms of cytoskeletal function. Actin is a common target of bacterial pathogens, but recent work also highlights the use of microtubules, cytoskeletal motors, intermediate filaments, and septins. The study of pathogen interactions with the cytoskeleton has illuminated key cellular processes such as phagocytosis, macropinocytosis, membrane trafficking, motility, autophagy, and signal transduction.

Electrostatics Control Actin Filament Nucleation and Elongation Kinetics

“…Listeria is a bacterial pathogen that hijacks the host actin cytoskeleton to move through the cytoplasm and escapes immune response by spreading from cell to cell without extracellular exposure. Listeria cells express ActA, an activator of the Arp2/3 complex, which then nucleates actin filaments at the surface of the bacteria, resulting in 'comet tails' composed of actin filaments that propel the bacteria forward (51). The intracellular speed of Listeria correlates directly with the rate of actin polymerization in cells (3), making it a direct readout of effects on actin polymerization.…”

Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism

“…In so doing, bacteria often resort to mimicry by expressing proteins that adopt core functions of key actin cytoskeletal components, particularly actin filament nucleation and elongation factors. However, bacterial proteins tend to bypass the elaborate regulatory networks characteristic of their eukaryotic counterparts, offering a rare opportunity to dissect their functions within a simplified system (2,3), with implications for our understanding of pathogenicity and the eukaryotic actin cytoskeleton alike.…”

“…passenger domain | translocator domain | spotted fever M any bacterial pathogens use the actin cytoskeleton of host eukaryotic cells for invasion and motility (1,2). In so doing, bacteria often resort to mimicry by expressing proteins that adopt core functions of key actin cytoskeletal components, particularly actin filament nucleation and elongation factors.…”

Membrane-deforming Proteins Play Distinct Roles in Actin Pedestal Biogenesis by Enterohemorrhagic Escherichia coli

“…For years, filamentous-actin (F-actin) 2 "comet tail" formation by Listeria monocytogenes and Shigella flexneri have served as powerful model systems for studying the mechanisms by which cells control cytoplasmic actin assembly (1,2). More recently, a group of extracellular pathogens that adhere to the cell surface and reorganize the underlying cytoskeleton into dynamic F-actin "pedestals" have been used to help decipher how cells regulate actin assembly during plasma membrane remodeling (3).…”