Rickettsia -Host-Tick Interactions: Knowledge Advances and Gaps

Infection and Immunity, Год журнала: 2022, Номер 90(9)

Опубликована: Авг. 22, 2022

Ticks are hematophagous ectoparasites capable of transmitting multiple human pathogens. Environmental changes have supported the expansion ticks into new geographical areas that become epicenters tick-borne diseases (TBDs).

Язык: Английский

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Lysine methylation shields an intracellular pathogen from ubiquitylation and autophagy

Science Advances, Год журнала: 2021, Номер 7(26)

Опубликована: Июнь 25, 2021

Lysine methylation camouflages a bacterial pathogen from the host ubiquitin attack.

Язык: Английский

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A patatin-like phospholipase mediates Rickettsia parkeri escape from host membranes

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июнь 27, 2022

Abstract Rickettsia species of the spotted fever group are arthropod-borne obligate intracellular bacteria that can cause mild to severe human disease. These invade host cells, replicate in cell cytosol, and spread from cell. To access cytosol avoid immune detection, they escape membrane-bound vacuoles by expressing factors disrupt membranes. Here, we show a patatin-like phospholipase A2 enzyme (Pat1) facilitates parkeri infection promoting membranes cell-cell spread. Pat1 is important for mouse model and, at cellular level, crucial efficiently escaping single double into avoiding galectins mark damaged also polyubiquitin, preventing recruitment autophagy receptor p62, actin-based motility

Язык: Английский

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Pathogenicity and virulence of Rickettsia

Virulence, Год журнала: 2022, Номер 13(1), С. 1752 - 1771

Опубликована: Окт. 8, 2022

Rickettsiae include diverse Gram-negative microbial species that exhibit obligatory intracellular lifecycles between mammalian hosts and arthropod vectors. Human infections with arthropod-borne Rickettsia continue to cause significant morbidity mortality as recent environmental changes foster the proliferation of vectors increased exposure humans. However, technical difficulties in working have delayed our progress understanding molecular mechanisms involved rickettsial pathogenesis disease transmission. Recent advances developing genetic tools for enabled investigators identify virulence genes, uncover functions, characterize host responses determinants. Therefore, continued efforts determine genes their biological functions will help us understand underlying associated rickettsioses.

Язык: Английский

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New insights into the impact of microbiome on horizontal and vertical transmission of a tick-borne pathogen

Microbiome, Год журнала: 2023, Номер 11(1)

Опубликована: Март 14, 2023

Abstract Background The impact of host skin microbiome on horizontal transmission tick-borne pathogens , and pathogen associated transstadial transovarial changes in tick are largely unknown, but important to control increasingly emerging diseases worldwide. Methods Focusing a rickettsiosis pathogen, Rickettsia raoultii we used R. -positive -negative Dermacentor spp. colonies study the involvement microbiota cutaneous infection with rickettsiae laboratory mice, function maintenance through all developmental stages (eggs, larvae, nymphs, adults) over two generations. Results We observed bacteria community, such as Chlamydia not only rickettsial colonization also feeding skin. diversity differed between paired tick-bitten un-bitten sites. For vertical transmission, significant differences pathogenic rickettsia chorts was across at least generations, which appeared be common pattern for another species, Candidatus tarasevichiae. More importantly, bacterial were complemented by functional shifts primed genetic information processing during blood feeding. Specifically, gene repertoire progenies enriched pathways metabolism hormone signals transmission. Conclusions demonstrate that might new factor determining ticks. While infect vertebrate hosts blood-feeding tick, they may manipulate maturation changing potential its tick’s life stages. findings here spur development new-generation methods ticks pathogens.

Язык: Английский

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Comparative virulence analysis of seven diverse strains ofOrientia tsutsugamushireveals a multifaceted and complex interplay of virulence factors responsible for disease

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 4, 2025

Abstract Orientia tsutsugamushi is an obligate intracellular bacterium found in Leptotrombidium mites that causes the human disease scrub typhus. A distinguishing feature of O. its extensive strain diversity, yet differences virulence between strains are not well defined nor understood. We sought to determine bacterial drivers pathogenicity by comparing murine infections using seven combined with epidemiological data rank each terms relative virulence. Murine cytokine expression revealed two most virulent strains, Ikeda and Kato, induced higher levels IL-6, IL-10, IFN-γ MCP-1 than other consistent increased these cytokines severe typhus patients. identify mechanistic basis observed differential their genomes, vitro growth properties cytokine/chemokine induction host cells. there was no single gene or group correlated virulence, clear pattern rate predicted disease. However, microscopy-based analysis infection cycle only fully avirulent our study, TA686, differed from all subcellular localisation surface protein ScaC. conclude distributed throughout genome, likely large varying arsenal effector proteins encoded different interact complex ways induce differing immune responses thus outcomes mammalian hosts. Author Summary Scrub a vector-borne caused tsutsugmushi spread mites. There numerous this some causing more humans others, do cause any illness at all. The factors driving understood, gaining insight into them could aid vaccine development help predict severity new isolates. To better typhus, we carried out experiments which compared diverse for animals. measured ability mice, so reliably classify as model. then analysed various genomic biological aspects markers both mice humans. report here factor predicts whether will be pathogenic not, but process resulting activity multiple genes working together drive host, either clearance bacteria escalating Future work exploring relationship disentangle detail.

Язык: Английский

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

mBio, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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

Язык: Английский

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Phosphatidylserine-binding receptor, CD300f, on macrophages mediates host invasion of pathogenic and non-pathogenic rickettsiae

Infection and Immunity, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Some arthropod-borne obligate intracellular rickettsiae are among the most virulent human pathogens. Rickettsia species modulate immune (e.g., macrophages; MΦ) and non-immune cell endothelial cells) responses to create a habitable environment for host colonization. MΦ play crucial role in either terminating an infection at early stage or succumbing bacterial replication However, our understanding of how invade cells, including MΦ, remains poorly defined. In this study, we describe mechanism invasion by species, involving rickettsial phosphatidylserine (PS), as ligand, CD300f receptor on MΦ. Our data reveal that engulfment both pathogenic typhi (the etiologic agent murine typhus) rickettsii Rocky Mountain spotted fever) well non-pathogenic montanensis, is significantly reduced bone marrow-derived macrophages (BMDMΦ) from CD300f-/- mice, compared wild-type (WT) animals. Furthermore, mechanistic analysis suggests PS potential source CD300f-mediated vivo studies using WT C57BL/6J mice show animals protected against R. typhi- rickettsii-induced fatal rickettsiosis, which corroborates with level burden detected spleens mice. Adoptive transfer CD300f-expressing important mediators control rickettsiosis vivo. Collectively, findings previously unappreciated efferocytic receptor, CD300f, facilitate within host.

Язык: Английский

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Vaccine development: obligate intracellular bacteria new tools, old pathogens: the current state of vaccines against obligate intracellular bacteria

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Март 19, 2024

Obligate intracellular bacteria have remained those for which effective vaccines are unavailable, mostly because protection does not solely rely on an antibody response. Effective antibody-based vaccines, however, been developed against extracellular pathogens or toxins. Additionally, obligate evolved many mechanisms to subvert the immune response, making vaccine development complex. Much of what we know about protective immunity these has determined using infection-resolved cases and animal models that mimic disease. These studies laid groundwork antigen discovery, which, combined with recent advances in vaccinology, should allow safe efficacious vaccines. Successful elicit potent T cell memory responses, addition humoral responses. Furthermore, they ought be designed specifically induce strong cytotoxic CD8+ responses immunity. This review will describe potentially this group bacteria. argue novel delivery platforms used during Sars-CoV-2 pandemic excellent candidates produce once antigens discovered. We then look more into Rickettsiaceae , Coxiella burnetti Anaplasmataceae from infancy until today. included Chlamydia trachomatis related reviews written years.

Язык: Английский

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Innate immunity in rickettsial infections

Frontiers in Cellular and Infection Microbiology, Год журнала: 2023, Номер 13

Опубликована: Май 9, 2023

Rickettsial agents are a diverse group of alpha-proteobacteria within the order Rickettsiales, which possesses two families with human pathogens, Rickettsiaceae and Anaplasmataceae. These obligate intracellular bacteria most frequently transmitted by arthropod vectors, first step in pathogens' avoidance host cell defenses. Considerable study immune responses to infection those that result protective immunity have been conducted. Less has focused on initial events mechanism these avoid innate hosts survive propagate from cells. By evaluating major mechanisms evading immunity, range similarities among become apparent, including escape destruction phagolysosomes professional phagocytes, dampen cells or subvert signaling recognition pathways related apoptosis, autophagy, proinflammatory responses, microbes attach enter molecules trigger responses. To illustrate principles, this review will focus common rickettsial occur globally, Rickettsia species Anaplasma phagocytophilum.

Язык: Английский

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