Rickettsia parkeri forms extensive, stable contacts with the rough endoplasmic reticulum

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(3)

Published: Jan. 7, 2025

Upon invasion into the host cell, a subset of bacterial pathogens resides exclusively in cytosol. While previous research revealed how they reshape plasma membrane during invasion, subvert immune response, and hijack cytoskeletal dynamics to promote their motility, it was unclear if these also interacted with organelles this crowded intracellular space. Here, we examined obligate pathogen Rickettsia parkeri interacts endoplasmic reticulum (ER), large dynamic organelle spread throughout cell. Using live-cell microscopy transmission focused-ion-beam scanning electron microscopy, show that R. forms extensive contacts rough ER are ∼55 nm apart cover more than half surface. Depletion ER-specific tethers VAPA VAPB reduced rickettsia–ER contacts, were localized around rickettsiae. Overall, our findings illuminate an interkingdom contact uniquely mediated by rickettsiae mimics some characteristics traditional sites.

Language: Английский

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Molecular detection and prevalence of Anaplasma and Rickettsia species in rodents captured from wildlife-human interfaces in Iringa and Morogoro regions, Tanzania

Mammalia, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Abstract Rickettsia and Anaplasma are Gram-negative, nonmotile, obligate intracellular bacteria in the order les. While various studies have been conducted on these threatening pathogens humans domestic animals, potential role of small mammals as reservoir zoonotic transmission is poorly understood Tanzania. This study investigated prevalence identity infecting captured at wildlife-human interfaces Iringa Morogoro, A total 371 blood samples were analyzed using conventional PCR DNA fragment sequencing, targeting approximately 424 bp 16S rRNA gene for 383 citrate synthase ( gltA ) . spp. was detected 9.7 %, 6.74 % samples. Rattus rattus exhibited highest both (21.43 %) (28.57 %). Two species A. bovis ovis three R. asembonensis , felis typhi confirmed through sequence analysis. highlights presence rodents, indicating rodents maintenance pathogens, especially interfaces, also reports first time

Language: Английский

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An expanded genetic toolkit for inducible expression and targeted gene silencing in Rickettsia parkeri

Journal of Bacteriology, Journal Year: 2024, Volume and Issue: 206(7)

Published: June 6, 2024

Pathogenic species within the

Language: Английский

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The cell division protein FzlA performs a conserved function in diverse alphaproteobacteria

Journal of Bacteriology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

ABSTRACT In almost all bacteria, the tubulin-like GTPase FtsZ polymerizes to form a “Z-ring” that marks site of division. recruits other proteins, collectively known as divisome, together remodel and constrict envelope. Constriction is driven by peptidoglycan (PG) cell wall synthesis glycosyltransferase FtsW transpeptidase FtsI (FtsWI), but these enzymes require activation function. How recruitment division leads FtsWI constriction remains largely unknown. Previous work in our laboratory demonstrated an FtsZ-binding protein, FzlA, essential for alphaproteobacterium Caulobacter crescentus . Additionally, we found FzlA binds DNA translocase called FtsK, suggesting it may link chromosome segregation. conserved throughout Alphaproteobacteria has only been examined detail C. Here, explored whether function diverse Alphaproteobacteria. We assessed homologs from Rickettsia parkeri Agrobacterium tumefaciens , that, similar they bind directly localize midcell. The FtsZ-FzlA interaction interface conserved, each three species can any vitro Finally, determined A. fulfill when produced indicating conservation These results suggest serves important regulator coordinates segregation with envelope across IMPORTANCE Cell bacterial replication must be highly regulated ensure robust remodeling coordination genome daughter cells. plays major role regulating this process activating manner couples broadly Alphaproteobacteria, class bacteria. have shown indeed, biochemical interactions are Because Alphaproteobacterial human pathogens, understanding protein its interactome could present therapeutic benefits identifying potential antibiotic targets treat infections.

Language: Английский

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A conserved interaction between the effector Sca4 and host clathrin suggests additional contributions for Sca4 during rickettsial infection

Infection and Immunity, Journal Year: 2024, Volume and Issue: 92(12)

Published: Nov. 13, 2024

Intracellular bacterial pathogens deploy secreted effector proteins that manipulate diverse host machinery and pathways to promote infection. Although many effectors carry out a single function or interaction, there are growing number of capable interacting with multiple factors. However, few by arthropod-borne obligate intracellular

Language: Английский

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An expanded genetic toolkit for inducible expression and targeted gene silencing inRickettsia parkeri

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 15, 2024

ABSTRACT Pathogenic species within the Rickettsia genus are transmitted to humans through arthropod vectors and cause a spectrum of diseases ranging from mild life-threatening. Despite rickettsiae posing an emerging global health risk, genetic requirements their infectious life cycles remain poorly understood. A major hurdle toward building this understanding has been lack efficient tools for manipulation, owing technical difficulties associated with obligate intracellular nature. To end, we implemented Tet-On system enable conditional gene expression in parkeri . Using Tet-On, show inducible antibiotic resistance fluorescent reporter. We further used promoter screen ability R. express four variants catalytically dead Cas9 (dCas9). demonstrate that all dCas9 can be expressed CRISPR interference (CRISPRi)-mediated targeted knockdown. knockdown as well endogenous virulence factor sca2 Altogether, have developed systems CRISPRi-mediated first time rickettsiae, laying groundwork more scalable, mechanistic investigations into cycles. IMPORTANCE The spotted fever group contains vector-borne pathogenic bacteria neglected threats public health. Due nature development manipulation stunted, molecular underpinnings lifecycle Here, expand toolkit by introducing These allow relatively easy rickettsial expression. effectiveness these disrupting cycle using CRISPRi deplete factor. will crucial comprehensive detailed biology pathogenesis.

Language: Английский

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Hitchhiker’s Guide to Borrelia burgdorferi

Journal of Bacteriology, Journal Year: 2024, Volume and Issue: 206(9)

Published: Aug. 14, 2024

Don't Panic. In the nearly 50 years since discovery of Lyme disease,

Language: Английский

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Rickettsia rickettsiiencodes a secretory lipase that facilitates intracytosolic colonization in host cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

Abstract The key cellular processes required for rickettsial obligate intracellular lifestyle, include internalization by phagocytosis, regulation of trafficking, and evasion lysosomal destruction to establish an intracytosolic replication niche, remain poorly defined. Recent reports showed that phospholipases play important role in vacuolar escape, but their functions are dispensable depending on the host cell-type. Here, we report identification a highly conserved putative lipase containing Serine hydrolase motif (GXSXG), named RLip ( R ickettsia Lip ase). Our work reveals expression is cytotoxic yeast cells, genetically tractable heterologous model system. We demonstrate possesses enzymatic activity show lipid specificity towards phosphoinositide (PI)(3), PI(3,4,5)P 3 , PI(3,4)P 2 lesser extent PI(4,5)P . Further, found induced during infection pathogenic R. rickettsii while its low or undetectable parkeri (mild-pathogenic) montanensis (non-pathogenic), respectively, invasion. Intriguingly, enriched cytoplasmic fraction however, minimally retained rickettsiae themselves, suggesting synthesized then secreted into cell cytoplasm. Neutralization activity, antibody-blocking, significantly abrogated escape from bactericidal phagolysosomal fusion, plays critical facilitating colonization Importance Arthropod-borne diseases rise globally, presenting perilous threat humans livestock. However, our inadequate understanding how Rickettsia manipulates processes, including destruction, has impaired development effective therapeutic interventions. identify motif, demonstrates cytoplasm bacteria itself. fusion. In sum, data support mechanism which employs fusion order colonize host.

Language: Английский

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Deciphering Rickettsia conorii metabolic pathways: a treasure map to therapeutic targets

Biotechnology Notes, Journal Year: 2024, Volume and Issue: 6, P. 1 - 9

Published: Nov. 23, 2024

Language: Английский

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