Orientia and Rickettsia: different flowers from the same garden

Current Opinion in Microbiology, Journal Year: 2023, Volume and Issue: 74, P. 102318 - 102318

Published: April 18, 2023

Recent discoveries of basal extracellular Rickettsiales have illuminated divergent evolutionary paths to host dependency in later-evolving lineages. Family Rickettsiaceae, primarily comprised numerous protist- and invertebrate-associated species, also includes human pathogens from two genera, Orientia Rickettsia. Once considered sister taxa, these bacteria form distinct lineages with newly appreciated lifestyles morphological traits. Contrasting other rickettsial Anaplasmataceae, Rickettsia species do not reside host-derived vacuoles lack glycolytic potential. With only a few described mechanisms, strategies for commandeering glycolysis support cytosolic growth remain be discovered. While regulatory systems this unique mode intracellular parasitism are unclear, conjugative transposons provide insights that critical determining how obligate overtake eukaryotic cytosol.

Language: Английский

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Activation of automethylated PRC2 by dimerization on chromatin

Molecular Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Intracellular niche switching as host subversion strategy of bacterial pathogens

Current Opinion in Cell Biology, Journal Year: 2022, Volume and Issue: 76, P. 102081 - 102081

Published: April 26, 2022

Numerous bacterial pathogens "confine" themselves within host cells with an intracellular localization as main or exclusive niche. Many of them switch dynamically between a membrane-bound cytosolic lifestyle. This requires either membrane damage and/or repair the bacterial-containing compartment. Niche switching has profound consequences on how cell recognizes in time and space for elimination. Moreover, niche impacts bacteria communicate to obtain nutrients, it affects accessibility antibiotics. Understanding local environments cellular phenotypes that lead is critical developing new host-targeted antimicrobial strategies, potential shed light into fundamental processes.

Language: Английский

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The Rickettsia actin-based motility effectors RickA and Sca2 contribute differently to cell-to-cell spread and pathogenicity

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

Published: Jan. 17, 2025

Rickettsia parkeri is an obligate intracellular, tick-borne bacterial pathogen that can cause eschar-associated rickettsiosis in humans. R. invades host cells, escapes from vacuoles into the cytosol, and undergoes two independent modes of actin-based motility mediated by effectors RickA or Sca2. Actin-based enables bacteria to enter protrusions cell plasma membrane are engulfed neighboring cells. However, whether how Sca2 independently contribute cell-to-cell spread vitro pathogenicity vivo has been unclear. Using live imaging rickA::Tn sca2::Tn mutants, we discovered both different spread. Compared with Sca2-spread, RickA-spread involves formation longer exhibit larger fluctuations length take a time be We further compared roles following intradermal (i.d.) infection Ifnar1-/-; Ifngr1-/- mice carrying knockout mutations genes encoding receptors for IFN-I (Ifnar1) IFN-γ (Ifngr1), which eschars succumb wild-type (WT) parkeri. observed important severe eschar formation, whereas contributes foci skin dissemination internal organs. Our results suggest drive distinct forms differently mammalian host.IMPORTANCERickettsia parkeri, bacterium spotted fever group species, transmitted ticks humans, leading symptoms including fever, rash, muscle aches, lesion at site tick bite. During infection, invade cells within animal host, proliferate cell's move using process called motility, unusual having proteins mediate motility. The significance our research reveal each these between signs mouse model disease. understanding contribution as well other viral pathogens require this

Language: Английский

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CSP ubiquitylation favours Plasmodium berghei survival during early liver stage infection

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 25, 2025

The circumsporozoite protein (CSP), an essential that covers the surface of Plasmodium sporozoite, is a key player in multiple stages parasite development within mosquito and during interactions between sporozoites mammalian hepatocytes. Here, we identify novel function berghei CSP: preventing elimination early hepatic infection, through its ubiquitylation at two lysine (K) residues, K252 K258, located C-terminal domain. A transgenic line lacking these residues exhibited significant decrease infectivity, with parasites being eliminated 4 h after infection. reduced infectivity correlated increased association host autophagy markers, LC3 LAMP1, to parasitophorous vacuole membrane liver stage parasite. Notably, inhibiting pathway fully rescued mutant from elimination. Collectively, reveal strategy employed by evade clearance which relies on specific CSP results via autophagic lysosomal activity.

Language: Английский

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Ferroptosis and protein translation: emerging perspectives in the research of myocardial infraction

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: May 2, 2025

Myocardial infarction, as the principal type of ischemic heart disease, has currently become focus research on its prevention and treatment strategies. From perspective myocardial infarction pathogenesis, it is urgent to impede progression this disease improve diagnosis techniques. Ferroptosis, a form programmed cell death mechanistically distinct from apoptosis autophagy, implicated throughout pathogenesis infarction. Dysregulation protein translation leads abnormal expression, disruption cellular signaling, dysfunction, thereby disturbing normal function exacerbating progression. Consequently, clarifying mechanism dysregulation in ferroptosis during will enhance understanding In review, latest progress relationship between collected. The mechanisms by which they regulate are explored, current status role different stages introduced. These findings expected provide valuable insights for pathophysiological precise treatment.

Language: Английский

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Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Aug. 23, 2021

Arthropod-borne rickettsial pathogens cause mild and severe human disease worldwide. The tick-borne pathogen Rickettsia parkeri elicits skin lesions (eschars) disseminated in humans; however, inbred mice are generally resistant to infection. We report that intradermal infection of lacking both interferon receptors (Ifnar1-/-;Ifngr1-/-) with as few 10 R. eschar formation disseminated, lethal disease. Similar infection, eschars exhibited necrosis inflammation, bacteria primarily found leukocytes. Using this model, we find the actin-based motility factor Sca2 is required for dissemination from internal organs, outer membrane protein OmpB contributes formation. Immunizing Ifnar1-/-;Ifngr1-/- sca2 ompB mutant protects against rechallenge, revealing live-attenuated vaccine candidates. Thus, a tractable model investigate rickettsiosis, virulence factors, immunity. Our results further suggest discrepancies between mouse susceptibility may be due differences signaling.

Language: Английский

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Critical roles of Rickettsia parkeri outer membrane protein B (OmpB) in the tick host

Infection and Immunity, Journal Year: 2024, Volume and Issue: 92(2)

Published: Jan. 11, 2024

ABSTRACT Rickettsia parkeri is a pathogen of public health concern and transmitted by the Gulf Coast tick, Amblyomma maculatum . Rickettsiae are obligate intracellular bacteria that enter replicate in diverse host cells. Rickettsial outer membrane protein B (OmpB) functions bacterial adhesion, invasion, avoidance cell-autonomous immunity mammalian cell infection, but function OmpB arthropod infection unknown. In this study, R. was evaluated tick host. wild-type ompB STOP ::tn (non-functional OmpB) were capillary fed to naïve A. ticks investigate dissemination transmission vertebrates. Ticks exposed had greater rickettsial loads all organs than at 12 h post-capillary feeding after 1 day on rats -infected ticks, dermal inflammation bite site less compared wild-type-infected ticks. vitro , attachment cells reduced, invasion mutant initially reduced eventually returned level 90 min post-infection. similar growth kinetics cells, suggesting not essential for replication These results indicate internalization pathogenicity during infection.

Language: Английский

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Pseudomonas aeruginosa Alters Peptidoglycan Composition under Nutrient Conditions Resembling Cystic Fibrosis Lung Infections

mSystems, Journal Year: 2022, Volume and Issue: 7(3)

Published: May 12, 2022

Epidemic strains of Pseudomonas aeruginosa are highly virulent opportunistic pathogens with increased transmissibility and enhanced antimicrobial resistance. Understanding the cellular mechanisms behind this heightened virulence resistance is critical. Peptidoglycan (PG) an integral component P. cells that essential to its survival a target for antimicrobials. Here, we examined global PG composition two epidemic strains, LESB58 LESlike1, compared them common laboratory PAO1 PA14. We also changes in when were cultured under nutrient conditions resembled cystic fibrosis lung infections. identified 448 unique muropeptides provide first evidence stem peptides modified O-methylation, meso-diaminopimelic acid (mDAP) deamination, novel substitutions mDAP residues within PG. Our results present both d,l- l,d-endopeptidase activity on sacculus Gram-negative organism. The varied significantly grown resembling (CF) infections, showing increases O-methylated decreases as well abundance de-N-acetylated sugars l,d-transpeptidase activity, which related bacterial antibiotic resistance, respectively. strain-specific where LESlike1 addition amino acids terminus peptide amidase activity. Overall, study demonstrates primarily influenced by mimic CF lung; however, inherent strain-to-strain differences exist. IMPORTANCE Using peptidoglycomics examine peptidoglycan allows insights into enzymatic functions important biopolymer. Changes structure have implications numerous physiological processes, including identification modifications illustrates complexity biopolymer aeruginosa. Analyzing clinical provides these difficult-to-eradicate

Language: Английский

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The Ankyrin Repeat Protein RARP-1 Is a Periplasmic Factor That Supports Rickettsia parkeri Growth and Host Cell Invasion

Journal of Bacteriology, Journal Year: 2022, Volume and Issue: 204(7)

Published: June 21, 2022

Rickettsia spp. are obligate intracellular bacterial pathogens that have evolved a variety of strategies to exploit their host cell niche. However, the factors contribute this lifestyle poorly understood. Here, we show conserved ankyrin repeat protein RARP-1 supports parkeri infection. Specifically, promotes efficient entry and growth within cytoplasm, but it is not necessary for cell-to-cell spread or evasion autophagy. We further demonstrate secreted into cytoplasm by R. parkeri. Instead, resides in periplasm, identify several binding partners predicted work concert with during Altogether, our data reveal plays critical role rickettsial life cycle. IMPORTANCERickettsia pose growing threat human health. Nevertheless, strict reliance on niche has hindered investigation molecular mechanisms driving This study yields much-needed insight RARP-1, which across genus yet been functionally characterized. Earlier had suggested cytoplasm. results from periplasm important both invasion cells These as novel regulator

Language: Английский

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