Actin-based motility of bacterial pathogens: mechanistic diversity and its impact on virulence

Abstract

A diverse spectrum of intracellular bacterial pathogens that inhabit the cytosol have evolved the ability to polymerize actin on their surface to power intracellular actin-based motility (ABM). These include species of Listeria, Burkholderia and Rickettsia, as well as Shigella and Mycobacteria Here, we provide an overview of the roles of bacterial ABM in survival and virulence. Moreover, we survey the molecular mechanisms of actin polymerization in host cells and describe how bacterial pathogens mimic or harness the full diversity of these mechanisms for ABM. Finally, we present ABM through a new lens by comparing motility mechanisms between related species of Listeria, Burkholderia, and Rickettsia Through these comparisons, we hope to illuminate how exploitation of different actin polymerization mechanisms influences ABM as well as pathogenicity and virulence in humans and other animals.

Keywords: Bacterial pathogen; Burkholderia; Listeria; Rickettsia; actin-based motility; cytoskeleton.

Figure 1.

Actin assembly and ABM play several roles in infection. Actin (orange) is mobilized during multiple stages of infection by intracellular pathogens (green). Actin facilitates bacterial invasion of the host cell. For bacterial pathogens that escape the vacuole into the cytosol, the recruitment of actin and/or actin-interacting proteins on the bacterial surface can influence its susceptibility to autophagy. Moreover, actin assembly powers bacterial ABM through the host cytosol, enabling bacteria to reach the cell periphery, where they enter into protrusions that are engulfed by neighboring cells or promote cell–cell fusion.

Figure 2.

Eukaryotic actin nucleators and their bacterial mimics. (A) Spontaneous nucleation of actin (orange) involves the formation of a trimer (red), which is kinetically unfavorable. Once a trimer forms, the filament can elongate (or shrink) at both the barbed (+) end or pointed (–) end, although elongation (and shrinking) is faster at the barbed end. (B) Four types of host proteins promote actin nucleation and/or elongation, including the Arp2/3 complex (yellow) and NPFs (blue), formins (yellow) and profilin (magenta), Ena/VASP proteins (yellow), and tandem-WH2-based nucleators (yellow). (C) Bacterial proteins (green) mimic or recruit each different class of host actin-polymerizing proteins (yellow and blue). (D) Representation of actin filament organization in actin tails (orange) corresponding to the bacterial genera and/or species indicated in (C).

Figure 3.

Species differences in actin assembly proteins. (A) Select species within the genera Listeria, Burkholderia and Rickettsia are represented according to their evolutionary relationships as determined by molecular phylogenetic analyses (branch lengths shown do not indicate evolutionary distances). Asterisk (*) denotes pathogenic species. (B) Schematic representations of bacterial ABM proteins are grouped to show domain comparisons between orthologs (see domain key below).