scholarly journals Significant Growth by Rickettsia Species within Human Macrophage-Like Cells Is a Phenotype Correlated with the Ability to Cause Disease in Mammals

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 228
Author(s):  
M. Nathan Kristof ◽  
Paige E. Allen ◽  
Lane D. Yutzy ◽  
Brandon Thibodaux ◽  
Christopher D. Paddock ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Spotted Fever ◽  
Growth Characteristic ◽  
Human Macrophage ◽  
Rickettsia Conorii ◽  
Spotted Fever Group ◽  
Rocky Mountain Spotted Fever ◽  
Phagocytic Cells ◽  
Pathogenic Potential ◽  
Rickettsia Species

Rickettsia are significant sources of tick-borne diseases in humans worldwide. In North America, two species in the spotted fever group of Rickettsia have been conclusively associated with disease of humans: Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, and Rickettsia parkeri, the cause of R. parkeri rickettsiosis. Previous work in our lab demonstrated non-endothelial parasitism by another pathogenic SFG Rickettsia species, Rickettsia conorii, within THP-1-derived macrophages, and we have hypothesized that this growth characteristic may be an underappreciated aspect of rickettsial pathogenesis in mammalian hosts. In this work, we demonstrated that multiple other recognized human pathogenic species of Rickettsia, including R. rickettsii, R. parkeri, Rickettsia africae, and Rickettsiaakari can grow within target endothelial cells as well as within PMA-differentiated THP-1 cells. In contrast, Rickettsia bellii, a Rickettsia species not associated with disease of humans, and R. rickettsii strain Iowa, an avirulent derivative of pathogenic R. rickettsii, could invade both cell types but proliferate only within endothelial cells. Further analysis revealed that similar to previous studies on R. conorii, other recognized pathogenic Rickettsia species could grow within the cytosol of THP-1-derived macrophages and avoided localization with two different markers of lysosomal compartments; LAMP-2 and cathepsin D. R. bellii, on the other hand, demonstrated significant co-localization with lysosomal compartments. Collectively, these findings suggest that the ability of pathogenic rickettsial species to establish a niche within macrophage-like cells could be an important factor in their ability to cause disease in mammals. These findings also suggest that analysis of growth within mammalian phagocytic cells may be useful to predict the pathogenic potential of newly isolated and identified Rickettsia species.

Rickettsial Diseases

2017 ◽  
Author(s):  
Lisa Sun ◽  
Michael V. Johnston
Keyword(s):  
Endothelial Cells ◽  
Q Fever ◽  
Spotted Fever ◽  
The United States ◽  
Dermacentor Variabilis ◽  
Farm Animals ◽  
Spotted Fever Group ◽  
Rocky Mountain Spotted Fever ◽  
The World ◽  
The Brain

Tick-borne rickettsioses are emerging as more important health problems throughout the world. The spotted fever group including Rickettsia rickettsia can cause encephalopathy, meningitis and brain damage by selectively targeting capillary endothelial cells in the brain, and stimulating inflammation, capillary leakage, hemorrhage, and intravascular coagulation. Rickettsia are are arthropod-borne gram-negative coccobacilli bacteria and are obligate intracellular organisms that do not survive in artificial medium. In North and South America, the most common rickettsial disorder is rocky mountain spotted fever (RMSF) transmitted by the dog tick Dermacentor variabilis or the wood tick Dermacentor andersoni. A characteristic “starry sky” pattern can be seen on MRI imaging of the brain in some patients with RMSF encephalopathy and is thought to reflect the organisms targeting of brain endothelial cells in capillaries the white matter. Early treatment with doxycycline is curative and reverses signs of encephalopathy if given within a few day of onset, but delayed treatment can be associated with permanent neurological disability. The typhus group of rickettsia bacteria include R. prowazekii, which causes epidemic typhus and R. typhi, which causes murine typhus (endemic) typhus in tropical and subtropical parts of the world. Flying squirrels and humans carry R prowazekii and rats are carry R. typhi. Q fever caused by the rickettsia organism Coxiella burnetti is transmitted from farm animals including sheep and is seen throughout the world including the United States.

Rickettsiosis

2015 ◽  
Author(s):  
Emmanuel A. Burdmann ◽  
Vivekanad Jha
Keyword(s):  
Serum Creatinine ◽  
Spotted Fever ◽  
Renal Involvement ◽  
Adverse Outcomes ◽  
Rickettsia Conorii ◽  
Mediterranean Spotted Fever ◽  
Spotted Fever Group ◽  
Rocky Mountain Spotted Fever ◽  
Murine Typhus ◽  
Epidemic Typhus

Rickettsiae are obligate intracellular bacteria transmitted by arthropods to a vertebrate host. Clinically relevant rickettsioses have a similar clinical pattern, manifesting as an acute febrile disease accompanied by headache, articular and muscle pain, and malaise.Epidemic typhus is a worldwide distributed disease caused by the Rickettsia prowazekii, with a human louse as a vector. Data on epidemic typhus-related renal injury is extremely scarce.Murine typhus is caused by the Rickettsia typhi and has a rodent flea as the vector. It is one of the most frequent rickettsioses, and is usually a self-limited febrile illness. Proteinuria, haematuria, elevations in serum creatinine (SCr) and/or blood urea nitrogen (BUN) and AKI have been reported. The real frequency of renal involvement in murine typhus is unknown. Renal abnormalities recover after the infectious disease resolution.Scrub typhus, caused by the Orientia tsutsugamushi, has the Leptotrombidium mite larva as vector. It is endemic in the Tsutsugamushi triangle delimited by Japan, Australia, India, and Siberia. It can manifest either as a self-limiting disease or as a severe, life-threatening multiorgan illness. Early administration of adequate antibiotics is essential to prevent adverse outcomes. Proteinuria, haematuria, and acute kidney injury (AKI) are frequent.Tick-borne rickettsioses are caused by bacteria from the spotted fever group and have ticks as vectors. Rocky Mountain spotted fever (RMSF) is caused by Rickettsia rickettsii. It is the most severe of the spotted fever rickettsial diseases, causing significant morbidity and lethality. RMSF occurs in North, Central, and South America. Renal impairment is frequent in severe forms of RMSF. Mediterranean spotted fever is caused by Rickettsia conorii, and is endemic in the Mediterranean area. It is usually a benign disease, but may have a severe course, clinically similar to RMSF. Haematuria, proteinuria, increased serum creatinine, and AKI may occur. Japanese spotted fever is caused by Rickettsia japonica. Lethal cases are reported yearly and AKI has occurred in the context of multiple organ failure.

scholarly journals Activation of Mechanistic Target of Rapamycin (mTOR) in Human Endothelial Cells Infected with Pathogenic Spotted Fever Group Rickettsiae

2020 ◽  
Vol 21 (19) ◽  
pp. 7179
Author(s):  
Abha Sahni ◽  
Hema P. Narra ◽  
Sanjeev K. Sahni
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase ◽  
Spotted Fever ◽  
Target Of Rapamycin ◽  
Spotted Fever Group ◽  
Microvascular Endothelium ◽  
Rickettsia Species ◽  
Mechanistic Target Of Rapamycin ◽  
P70 S6k

Attributed to the tropism for host microvascular endothelium lining the blood vessels, vascular inflammation and dysfunction represent salient features of rickettsial pathogenesis, yet the details of fundamentally important pathogen interactions with host endothelial cells (ECs) as the primary targets of infection remain poorly appreciated. Mechanistic target of rapamycin (mTOR), a serine/threonine protein kinase of the phosphatidylinositol kinase-related kinase family, assembles into two functionally distinct complexes, namely mTORC1 (Raptor) and mTORC2 (Rictor), implicated in the determination of innate immune responses to intracellular pathogens via transcriptional regulation. In the present study, we investigated activation status of mTOR and its potential contributions to host EC responses during Rickettsia rickettsii and R. conorii infection. Protein lysates from infected ECs were analyzed for threonine 421/serine 424 phosphorylation of p70 S6 kinase (p70 S6K) and that of serine 2448 on mTOR itself as established markers of mTORC1 activation. For mTORC2, we assessed phosphorylation of protein kinase B (PKB or Akt) and protein kinase C (PKC), respectively, on serine 473 and serine 657. The results suggest increased phosphorylation of p70 S6K and mTOR during Rickettsia infection of ECs as early as 3 h and persisting for up to 24 h post-infection. The steady-state levels of phospho-Akt and phospho-PKC were also increased. Infection with pathogenic rickettsiae also resulted in the formation of microtubule-associated protein 1A/1B-light chain 3 (LC3-II) puncta and increased lipidation of LC3-II, a response significantly inhibited by introduction of siRNA targeting mTORC1 into ECs. These findings thus yield first evidence for the activation of both mTORC1 and mTORC2 during EC infection in vitro with Rickettsia species and suggest that early induction of autophagy in response to intracellular infection might be regulated by this important pathway known to function as a central integrator of cellular immunity and inflammation.

scholarly journals New Spotted Fever Group Rickettsia Isolate, Identified by Sequence Analysis of Conserved Genomic Regions

Pathogens ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 11
Author(s):  
Dar Klein ◽  
Adi Beth-Din ◽  
Regev Cohen ◽  
Shirley Lazar ◽  
Itai Glinert ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Spotted Fever ◽  
Diagnostic Procedures ◽  
Clinical Samples ◽  
Severe Illness ◽  
Rickettsia Conorii ◽  
Spotted Fever Group ◽  
Rickettsia Species ◽  
Questing Ticks ◽  
Absolute Identity

The clinical features of spotted fever group (SFG) Rickettsia induced disease range from a mild to severe illness. The clinical complexity is even greater due to the fact that the disease can be caused by different species with varying degrees of virulence. Current knowledge asserts that the Israeli SFG (ISF) strain Rickettsia conorii israelensis is the only human pathogenic SFG member in Israel. Current diagnostic procedures distinguish between SFG and the typhus group rickettsiosis, assuming all SFG-positive clinical samples positive for ISF. Molecular studies on questing ticks over the past decade have uncovered the existence of other SFG strains besides ISF in Israel and the region. This study describes the first documented analysis of SFG-positive samples from Israeli patients with the goal of distinguishing between ISF and non-ISF SFG strains. We managed to identify a new Rickettsia isolate from three independent clinical samples in Israel which was shown to be an as-yet unknown SFG member, showing no absolute identity with any known Rickettsia species present in the NCBI database.

scholarly journals Molecular Detection of Spotted Fever Group Rickettsiae (Rickettsiales: Rickettsiaceae) in Dermacentor variabilis (Acari: Ixodidae) Collected Along the Platte River in South Central Nebraska

2019 ◽  
Vol 57 (2) ◽  
pp. 519-523
Author(s):  
Brandon E Luedtke ◽  
Julie J Shaffer ◽  
Estrella Monrroy ◽  
Corey W Willicott ◽  
Travis J Bourret
Keyword(s):  
Spotted Fever ◽  
Rocky Mountain ◽  
Dermacentor Variabilis ◽  
Amblyomma Americanum ◽  
Spotted Fever Group ◽  
Rocky Mountain Spotted Fever ◽  
Rickettsia Species ◽  
Platte River ◽  
Rickettsia Rickettsii ◽  
South Central

Abstract Dermacentor variabilis is the predominant tick species in Nebraska and is presumed to be the primary vector of Rickettsia rickettsii associated with cases of Rocky Mountain spotted fever (RMSF). Interestingly, RMSF cases in Nebraska have increased on a year-to-year basis, yet the prevalence of R. rickettsii in D. variabilis ticks has not been established for Nebraska. Here we sought to set a baseline for the prevalence of R. rickettsii and other spotted fever group (SFG) rickettsiae harbored by D. variabilis ticks. Over a 3-yr period, D. variabilis were collected along the Platte River in south central Nebraska. Individual tick DNA was analyzed using endpoint PCR to identify ticks carrying SFG rickettsiae. In total, 927 D. variabilis were analyzed by PCR and 38 (4.1%) ticks tested positive for SFG rickettsiae. Presumptive positives were sequenced to identify the Rickettsia species, of which 29 (76%) were R. montanensis, 5 (13%) were R. amblyommatis, 4 (11%) were R. bellii, and R. rickettsii was not detected. These data indicate that R. rickettsii is likely at a low prevalence in south central Nebraska and spillover of R. amblyommatis into D. variabilis is likely occurring due to the invasive lone star tick (Amblyomma americanum). In addition, our data suggest that R. montanensis and R. amblyommatis could be associated with the increase in SFG rickettsiae infections in Nebraska. This information will be of value to clinicians and the general public for evaluating diagnosis of disease- and risk-associated environmental exposure, respectively.

scholarly journals Suppressor of cytokine signalling protein SOCS1 and UBP43 regulate the expression of type I interferon-stimulated genes in human microvascular endothelial cells infected with Rickettsia conorii

2013 ◽  
Vol 62 (7) ◽  
pp. 968-979 ◽  
Author(s):  
Punsiri M. Colonne ◽  
Abha Sahni ◽  
Sanjeev K. Sahni
Keyword(s):  
Endothelial Cells ◽  
Transcriptional Activation ◽  
Spotted Fever ◽  
Microvascular Endothelial Cells ◽  
Rickettsia Conorii ◽  
Type I ◽  
Spotted Fever Group ◽  
Dependent Manner ◽  
Microvascular Endothelium ◽  
Microvascular Endothelial

Rickettsia conorii, the causative agent of Mediterranean spotted fever, preferentially infects human microvascular endothelium and activates pro-inflammatory innate immune responses as evidenced by enhanced expression and secretion of cytokines and chemokines. Our recent studies reveal that human microvascular endothelial cells (HMECs) infected with R. conorii also launch ‘antiviral’ host defence mechanisms typically governed by type I interferons. To summarize, infected HMECs secrete IFN-β to activate STAT1 in an autocrine/paracrine manner and display increased expression of IFN-stimulated genes, for example ISG15, which in turn activate innate responses to interfere with intracellular replication of rickettsiae. We now present evidence that UBP43 and SOCS1, known negative regulators of JAK/STAT signalling, are also induced in R. conorii-infected HMECs, of which UBP43 but not SOCS1 functions to negatively regulate STAT1 activation. Interestingly, UBP43 induction is almost completely abolished in the presence of IFN-β-neutralizing antibody, implicating an important role for UBP43 as a feedback inhibitor for IFN-β-mediated STAT1 activation. In contrast, SOCS1 expression is only partially affected by IFN-β neutralization, implicating potential involvement of as-yet-unidentified IFN-independent mechanism(s) in SOCS1 induction during R. conorii infection. A number of IFN-stimulated genes, including ISG15, OAS1, MX1, IRF1, IRF9 and TAP1 are also induced in an IFN-β-dependent manner, whereas GBP1 remains unaffected by IFN-β neutralization. Increased STAT1 phosphorylation in HMECs subjected to UBP43 knockdown led to transcriptional activation of OAS1, MX1 and GBP1, confirming the negative regulatory role of UBP43. Although IRF1, IRF9 and TAP1 were induced by IFN-β, siRNA-mediated silencing of UBP43 or SOCS1 did not significantly affect their transcriptional activation. Expression of ISG15 was, however, increased in HMECs transfected with siRNA for UBP43 and SOCS1. Thus, unique regulatory patterns of induced expression of UBP43, SOCS1 and IFN-stimulated genes represent pathogen-specific responses underlying IFN-β-mediated host endothelial signalling during the pathogenesis of spotted fever group rickettsiosis.

scholarly journals Identification and Characterization of “Candidatus Rickettsia Thierseensis”, a Novel Spotted Fever Group Rickettsia Species Detected in Austria

2020 ◽  
Vol 8 (11) ◽  
pp. 1670
Author(s):  
Anna-Margarita Schötta ◽  
Michiel Wijnveld ◽  
Dieter Höss ◽  
Gerold Stanek ◽  
Hannes Stockinger ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
Spotted Fever ◽  
Intergenic Spacer ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Species Discrimination ◽  
Spotted Fever Group ◽  
Pathogenic Potential ◽  
Rickettsia Species ◽  
Intergenic Spacer Region ◽  
Sfg Rickettsia

Rickettsia spp. are the second most common pathogens detected in Ixodes ricinus ticks in Austria after Borrelia burgdorferi sensu lato. Species belonging to the spotted fever group (SFG) are the causative agents for tick-borne rickettsiosis across the world. So far, only four SFG Rickettsia spp. were detected in Austria, namely R. helvetica, R. raoultii, R. monacensis and R. slovaca. Here, we describe the identification of a new SFG Rickettsia species detected in an I. ricinus tick. Sequencing of various rickettsial genes revealed a nucleotide sequence similarity of 99.6%, 98.5%, 97.3% and 98.5% to the gltA, ompA, ompB, and sca4 genes, respectively, of known and validated species. Additionally, sequencing of the htrA gene and 23S-5S intergenic spacer region also only showed 99.6% and 99.2%, respectively, similarity to known species. Therefore, and in accordance with current criteria for Rickettsia species discrimination, we hereby describe a new species of the SFG with putative pathogenic potential. We propose the name “Candidatus Rickettsia thierseensis” based on the village Thiersee in the Austrian province of Tyrol, where the carrying tick was found.

Mitbringsel aus den Ferien

Praxis ◽  
2005 ◽  
Vol 94 (47) ◽  
pp. 1869-1870
Author(s):  
Balestra ◽  
Nüesch
Keyword(s):  
Rocky Mountains ◽  
Spotted Fever ◽  
Rocky Mountain ◽  
Rickettsia Conorii ◽  
Rocky Mountain Spotted Fever ◽  
Klinische Diagnose ◽  
Rickettsia Rickettsii

Eine 37-jährige Patientin stellt sich nach der Rückkehr von einer Rundreise durch Nordamerika mit einem Status febrilis seit zehn Tagen und einem makulösem extremitätenbetontem Exanthem seit einem Tag vor. Bei suggestiver Klinik und Besuch der Rocky Mountains wird ein Rocky Mountain spotted fever diagnostiziert. Die Serologie für Rickettsia conorii, die mit Rickettsia rickettsii kreuzreagiert, war positiv und bestätigte die klinische Diagnose. Allerdings konnte der beweisende vierfache Titeranstieg, möglicherweise wegen spät abgenommener ersten Serologie, nicht nachgewiesen werden. Nach zweiwöchiger antibiotischer Therapie mit Doxycycline waren Status febrilis und Exanthem regredient.

scholarly journals Quantitative Analyses of Variations in the Injury of Endothelial Cells Elicited by 11 Isolates of Rickettsia rickettsii

2001 ◽  
Vol 8 (4) ◽  
pp. 788-796 ◽  
Author(s):  
Marina E. Eremeeva ◽  
Gregory A. Dasch ◽  
David J. Silverman
Keyword(s):  
North Carolina ◽  
Endothelial Cells ◽  
Reduced Glutathione ◽  
Spotted Fever ◽  
Ixodid Ticks ◽  
Spotted Fever Group ◽  
Cellular Injury ◽  
Rickettsia Rickettsii ◽  
Cytopathic Effects ◽  
Group I

ABSTRACT Eleven isolates of spotted fever group rickettsiae from the blood of patients or ixodid ticks from North and South America were characterized. All isolates were identified as Rickettsia rickettsii using restriction fragment length polymorphism analysis of a 532-bp rOmpA gene fragment obtained by PCR. The ability of the R. rickettsii isolates to elicit cytopathic effects and parameters of oxidative injury were examined in cultured human EA.hy 926 endothelial cells. Cytopathic effects were determined by direct observation of infected cultures, by measuring the release of cytoplasmic lactate dehydrogenase (LDH), and by determination of intracellular pools of peroxide and reduced glutathione. Four biotypes of R. rickettsii were defined. Group I included two highly cytopathic isolates from Montana, Bitterroot and Sheila Smith, and three isolates from Maryland, North Carolina, and Brazil. These isolates rapidly damaged cells, released large amounts of cytoplasmic LDH, caused accumulation of intracellular peroxide, and depleted intracellular pools of reduced glutathione. Group II contained three isolates, two from Montana, Hlp#2 and Lost Horse Canyon, and an isolate from Colombia, which were similar to group I but caused either lower responses in LDH release or smaller changes in intracellular peroxide levels. The group III isolates, Sawtooth from Montana and 84JG from North Carolina, caused lower cellular injury by all measures. Group IV isolate Price T from Montana was the least cytopathic and caused minimal alterations of all parameters measured. Understanding the molecular basis for the varied cellular injury caused by different isolates of R. rickettsii may contribute to improved treatment of Rocky Mountain spotted fever and to the rapid identification of those isolates which are more likely to cause fulminant disease.

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