Functional Mimicry of Eukaryotic Actin Assembly by Pathogen Effector Proteins

Abstract

The actin cytoskeleton lies at the heart of many essential cellular processes. There are hundreds of proteins that cells use to control the size and shape of actin cytoskeletal networks. As such, various pathogens utilize different strategies to hijack the infected eukaryotic host actin dynamics for their benefit. These include the control of upstream signaling pathways that lead to actin assembly, control of eukaryotic actin assembly factors, encoding toxins that distort regular actin dynamics, or by encoding effectors that directly interact with and assemble actin filaments. The latter class of effectors is unique in that, quite often, they assemble actin in a straightforward manner using novel sequences, folds, and molecular mechanisms. The study of these mechanisms promises to provide major insights into the fundamental determinants of actin assembly, as well as a deeper understanding of host–pathogen interactions in general, and contribute to therapeutic development efforts targeting their respective pathogens. This review discusses mechanisms and highlights shared and unique features of actin assembly by pathogen effectors that directly bind and assemble actin, focusing on eukaryotic actin nucleator functional mimics Rickettsia Sca2 (formin mimic), Burkholderia BimA (Ena/VASP mimic), and Vibrio VopL (tandem WH2-motif mimic).

Brucella NpeA is a secreted Type IV effector containing an N-WASP-binding short linear motif that promotes niche formation

“…To exploit host cell signaling pathways, many bacteria have effector proteins with eukaryotic-like domains that facilitate protein-protein interactions required for host cell subversion. Among these effectors, which have multiple potential targets, regulators of actin cytoskeletal dynamics are often represented ( 2 , 3 , 50 ). Although several steps of the intracellular cycle of Brucella are known with relative detail, the molecular interactions of Brucella with the host actin cytoskeleton are mostly unknown.…”

A Functional Yeast-Based Screen Identifies the Host Microtubule Cytoskeleton as a Target of Numerous Chlamydia pneumoniae Proteins

“…Thus, for obligate intracellular pathogens with an intracellular developmental cycle within a membrane-bound compartment, the rearrangement and repurposing of host cellular structures, such as the dynamic host cytoskeleton is required. While the modulation of the host actin cytoskeleton by bacterial pathogens is well studied (for reviews, see [6][7][8]), our knowledge of how the MT cytoskeleton is used and altered by pathogenic bacteria is scarce (for a review, see [9]). A few bacterial effector proteins were identified that alter MT dynamics, such as VirA from Shigella and EspG from E. coli (for a review, see [9]).…”