An obligate intracellular bacterial pathogen forms a direct, interkingdom membrane contact site

Acevedo-Sánchez, Yamilex; Woida, Patrick J.; Kräemer, Stephan; Lamason, Rebecca

doi:10.1101/2023.06.05.543771

Cited by 3 publications

(1 citation statement)

References 49 publications

(73 reference statements)

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“…N- terminally tagged SrfB, SrfC, and SrfE expressed poorly, so pRL0383, pRL0384, and pRL0386 respectively contain a C-terminal GGSGS DYKDHDGDYKDHDIDYKDDDDK sequence instead. FCW2IB-BiP-mNeonGreen-KDEL was generated as previously described 74 . pRL0389 was made by replacing the Lifeact-3xTagBFP insert in FCW2IB- Lifeact-3xTagBFP 4 with Gaussia -Dura luciferase from pCMV-Gaussia-Dura Luc (Thermo Fisher Scientific catalog number 16191).…”

Section: Methodsmentioning

confidence: 99%

Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen

Sanderlin,

Margolis,

Meyer

et al. 2023

Preprint

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Pathogenic bacteria secrete protein effectors to hijack host machinery and remodel their infectious niche.Rickettsiaspp. are obligate intracellular bacteria that can cause life- threatening disease, but their absolute dependence on the host cell environment has impeded discovery of rickettsial effectors and their host targets. We implemented bioorthogonal non-canonical amino acid tagging (BONCAT) duringR. parkeriinfection to selectively label, isolate, and identify secreted effectors. As the first use of BONCAT in an obligate intracellular bacterium, our screen more than doubles the number of experimentally validated effectors forR. parkeri. The novel secreted rickettsial factors (Srfs) we identified includeRickettsia-specific proteins of unknown function that localize to the host cytoplasm, mitochondria, and ER. We further show that one such effector, SrfD, interacts with the host Sec61 translocon. Altogether, our work uncovers a diverse set of previously uncharacterized rickettsial effectors and lays the foundation for a deeper exploration of the host-pathogen interface.

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Section: Methodsmentioning

confidence: 99%

Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen

Sanderlin,

Margolis,

Meyer

et al. 2023

Preprint

Self Cite

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Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen

Sanderlin,

Kurka Margolis,

Meyer

et al. 2024

Nat Commun

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Pathogenic bacteria secrete protein effectors to hijack host machinery and remodel their infectious niche. Rickettsia spp. are obligate intracellular bacteria that can cause life-threatening disease, but their absolute dependence on the host cell has impeded discovery of rickettsial effectors and their host targets. We implemented bioorthogonal non-canonical amino acid tagging (BONCAT) during R. parkeri infection to selectively label, isolate, and identify effectors delivered into the host cell. As the first use of BONCAT in an obligate intracellular bacterium, our screen more than doubles the number of experimentally validated effectors for the genus. The seven novel secreted rickettsial factors (Srfs) we identified include Rickettsia-specific proteins of unknown function that localize to the host cytoplasm, mitochondria, and ER. We further show that one such effector, SrfD, interacts with the host Sec61 translocon. Altogether, our work uncovers a diverse set of previously uncharacterized rickettsial effectors and lays the foundation for a deeper exploration of the host-pathogen interface.

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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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An obligate intracellular bacterial pathogen forms a direct, interkingdom membrane contact site

Cited by 3 publications

References 49 publications

Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen

Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen

Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen

Pathogenic Rickettsia spp. as emerging models for bacterial biology

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