Single particle cryo-EM analysis of Rickettsia conorii Sca2 reveals a formin-like core

Carman, Peter J.; Rębowski, Grzegorz; Domínguez, Roberto; Alqassim, Saif S.

doi:10.1016/j.jsb.2023.107960

Cited by 2 publications

(1 citation statement)

References 47 publications

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“…While many pathogenic actin-interacting effectors mimic the host actin assembly proteins (structurally or functionally), some toxins employ unique mechanisms of actin hijacking. The former group can be exemplified by the Rickettsia effector Sca2, which promotes filament barbed-end elongation similar to host formins [62,63]; Burkholderia BimA, which utilizes WH2 motifs and poly-proline-rich regions to nucleate, elongate, and bundle actin filaments mimicking host Ena/VASP proteins [56]; Chlamydia TARP, which binds to G-actin with its WH2-like domain and, upon oligomerization, nucleates new actin filaments imitating host WH2 domain-containing nucleators [64]. Vibrio VopF/L represent bacterial effectors, which employ an intricate combination of a unique pointed-end elongation mechanism [37] and a host-mimicking actin nucleation strategy [36].…”

Section: Discussionmentioning

confidence: 99%

Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH

et al. 2023

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L. pneumophila propagates in eukaryotic cells within a specialized niche, the Legionella-containing vacuole (LCV). The infection process is controlled by over 330 effector proteins delivered through the type IV secretion system. In this study, we report that the Legionella MavH effector localizes to endosomes and remodels host actin cytoskeleton in a phosphatidylinositol 3-phosphate (PI(3)P) dependent manner when ectopically expressed. We show that MavH recruits host actin capping protein (CP) and actin to the endosome via its CP-interacting (CPI) motif and WH2-like actin-binding domain, respectively. In vitro assays revealed that MavH stimulates actin assembly on PI(3)P-containing liposomes causing their tubulation. In addition, the recruitment of CP by MavH negatively regulates F-actin density at the membrane. We further show that, in L. pneumophila-infected cells, MavH appears around the LCV at the very early stage of infection and facilitates bacterium entry into the host. Together, our results reveal a novel mechanism of membrane tubulation induced by membrane-dependent actin polymerization catalyzed by MavH that contributes to the early stage of L. pneumophila infection by regulating host actin dynamics.

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Section: Discussionmentioning

confidence: 99%

Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH

et al. 2023

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Pathogenic Rickettsia spp. as emerging models for bacterial biology

Sit,

Lamason

2024

J Bacteriol

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Our understanding of free-living bacterial models like Escherichia coli far outpaces that of obligate intracellular bacteria, which cannot be cultured axenically. All obligate intracellular bacteria are host-associated, and many cause serious human diseases. Their constant exposure to the distinct biochemical niche of the host has driven the evolution of numerous specialized bacteriological and genetic adaptations, as well as innovative molecular mechanisms of infection. Here, we review the history and use of pathogenic Rickettsia species, which cause an array of vector-borne vascular illnesses, as model systems to probe microbial biology. Although many challenges remain in our studies of these organisms, the rich pathogenic and biological diversity of Rickettsia spp. constitutes a unique backdrop to investigate how microbes survive and thrive in host and vector cells. We take a bacterial-focused perspective and highlight emerging insights that relate to new host–pathogen interactions, bacterial physiology, and evolution. The transformation of Rickettsia spp. from pathogens to models demonstrates how recalcitrant microbes may be leveraged in the lab to tap unmined bacterial diversity for new discoveries. Rickettsia spp. hold great promise as model systems not only to understand other obligate intracellular pathogens but also to discover new biology across and beyond bacteria.

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Single particle cryo-EM analysis of Rickettsia conorii Sca2 reveals a formin-like core

Cited by 2 publications

References 47 publications

Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH

Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH

Pathogenic Rickettsia spp. as emerging models for bacterial biology

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