scholarly journals Vesicular spotted fever due to Rickettsia parkeri simulates the clinicopathologic features of rickettsialpox

2021 ◽  
Author(s):  
Ali Malik ◽  
Penelope Kallis ◽  
Clinton Enos ◽  
Addie Walker ◽  
Kiran Motaparthi
Keyword(s):  
Spotted Fever ◽  
Clinicopathologic Features ◽  
Rickettsia Parkeri

scholarly journals A streamlined method for transposon mutagenesis ofRickettsia parkeriyields numerous mutations that impact infection

2018 ◽  
Author(s):  
Rebecca L. Lamason ◽  
Natasha M. Kafai ◽  
Matthew D. Welch
Keyword(s):  
Host Cell ◽  
Virulence Factors ◽  
Vascular Endothelial Cells ◽  
Spotted Fever ◽  
Transposon Mutagenesis ◽  
Host Cells ◽  
Spotted Fever Group ◽  
Loss Of Function ◽  
Rickettsia Parkeri ◽  
Obligate Intracellular

AbstractThe rickettsiae are obligate intracellular alphaproteobacteria that exhibit a complex infectious life cycle in both arthropod and mammalian hosts. As obligate intracellular bacteria,Rickettsiaare highly adapted to living inside a variety of host cells, including vascular endothelial cells during mammalian infection. Although it is assumed that the rickettsiae produce numerous virulence factors that usurp or disrupt various host cell pathways, they have been challenging to genetically manipulate to identify the key bacterial factors that contribute to infection. Motivated to overcome this challenge, we sought to expand the repertoire of available rickettsial loss-of-function mutants, using an improvedmariner-based transposon mutagenesis scheme. Here, we present the isolation of over 100 transposon mutants in the spotted fever group speciesRickettsia parkeri. These mutants targeted genes implicated in a variety of pathways, including bacterial replication and metabolism, hypothetical proteins, the type IV secretion system, as well as factors with previously established roles in host cell interactions and pathogenesis. Given the need to identify critical virulence factors, forward genetic screens such as this will provide an excellent platform to more directly investigate rickettsial biology and pathogenesis.

scholarly journals A metabolic dependency for host isoprenoids in the obligate intracellular pathogenRickettsia parkeriunderlies a sensitivity for the statin class of host-targeted therapeutics

2019 ◽  
Author(s):  
Vida Ahyong ◽  
Charles A. Berdan ◽  
Daniel K. Nomura ◽  
Matthew D. Welch
Keyword(s):  
Cell Wall ◽  
Host Cell ◽  
Bacterial Growth ◽  
Spotted Fever ◽  
Intracellular Pathogens ◽  
Biosynthetic Pathways ◽  
Targeted Therapeutics ◽  
Rickettsia Parkeri ◽  
Obligate Intracellular ◽  
Intracellular Parasites

AbstractGram-negative bacteria in the order Rickettsiales are obligate intracellular parasites that cause human diseases such typhus and spotted fever. They have evolved a dependence on essential nutrients and metabolites from the host cell as a consequence of extensive genome streamlining. However, it remains largely unknown which nutrients they require and whether their metabolic dependency can be exploited therapeutically. Here, we describe a genetic rewiring of bacterial isoprenoid biosynthetic pathways in the Rickettsiales that has resulted from reductive genome evolution. We further investigated whether the spotted fever groupRickettsiaspeciesRickettsia parkeriscavenges isoprenoid precursors directly from the host. Using targeted mass spectrometry in uninfected and infected cells, we found decreases in host isoprenoid products and concomitant increases in bacterial isoprenoid metabolites. Additionally, we report that bacterial growth is prohibited by inhibition of the host isoprenoid pathway with the statins class of drugs. We show that growth inhibition correlates with changes in bacterial size and shape that mimic those caused by antibiotics that inhibit peptidoglycan biosynthesis, suggesting statins inhibit cell wall synthesis. Altogether, our results describe an Achilles’ heel of obligate intracellular pathogens that can be exploited with host-targeted therapeutics that interfere with metabolic pathways required for bacterial growth.ImportanceObligate intracellular parasites, which include viruses as well as certain bacteria and eukaryotes, extract essential nutrients and metabolites from their host cell. As a result, these pathogens have often lost essential biosynthetic pathways and are metabolically dependent on the host. In this study, we describe a metabolic dependency of the bacterial pathogenRickettsia parkerion host isoprenoid molecules that are used in the biosynthesis of downstream products including cholesterol, steroid hormones, and heme. Bacteria make products from isoprenoids such as an essential lipid carrier for making the bacterial cell wall. We show that bacterial metabolic dependency can represent an Achilles’ heel, and that inhibiting host isoprenoid biosynthesis with the FDA-approved statin class of drugs inhibits bacterial growth by interfering with the integrity of the cell wall. This work highlights a potential to treat infections by obligate intracellular pathogens through inhibition of host biosynthetic pathways that are susceptible to parasitism.

scholarly journals Serological evidence of Rickettsia parkeri as the etiological agent of rickettsiosis in Uruguay

2009 ◽  
Vol 51 (6) ◽  
pp. 337-339 ◽  
Author(s):  
Ismael A. Conti-Díaz ◽  
Jonas Moraes-Filho ◽  
Richard C. Pacheco ◽  
Marcelo B. Labruna
Keyword(s):  
Spotted Fever ◽  
Clinical Manifestations ◽  
The United States ◽  
Immunofluorescence Assay ◽  
Etiological Agent ◽  
Serological Evidence ◽  
Rickettsia Parkeri ◽  
Rickettsia Rickettsii ◽  
Antibody Absorption ◽  
Mild Fever

We report three new rickettsiosis human cases in Uruguay. The three clinical cases presented clinical manifestations similar to previous reported cases of Rickettsia parkeri in the United States; that is mild fever (< 40 ºC), malaise, headache, rash, inoculation eschar at the tick bite site, regional lymphadenopathy, and no lethality. Serological antibody-absorption tests with purified antigens of R. parkeri and Rickettsia rickettsii, associated with immunofluorescence assay indicated that the patients in two cases were infected by R. parkeri. Epidemiological and clinical evidences, coupled with our serological analysis, suggest that R. parkeri is the etiological agent of human cases of spotted fever in Uruguay, a disease that has been recognized in that country as cutaneous-ganglionar rickettsiosis.

scholarly journals Rickettsia parkeri in Amblyomma dubitatum ticks in a spotted fever focus from the Brazilian Pampa

Acta Tropica ◽  
2017 ◽  
Vol 171 ◽  
pp. 182-185 ◽  
Author(s):  
Bárbara Weck ◽  
Bruno Dall’Agnol ◽  
Ugo Souza ◽  
Anelise Webster ◽  
Bárbara Stenzel ◽  
...  
Keyword(s):  
Spotted Fever ◽  
Rickettsia Parkeri

scholarly journals Proteomic Analysis of Rickettsia parkeri Strain Portsmouth

2009 ◽  
Vol 77 (12) ◽  
pp. 5262-5271 ◽  
Author(s):  
Walairat Pornwiroon ◽  
Apichai Bourchookarn ◽  
Christopher D. Paddock ◽  
Kevin R. Macaluso
Keyword(s):  
Cell Surface ◽  
Vaccine Development ◽  
Spotted Fever ◽  
The United States ◽  
Trna Synthetase ◽  
Surface Proteins ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Two Dimensional ◽  
Rickettsia Parkeri

ABSTRACT Rickettsia parkeri, a recently recognized pathogen of human, is one of several Rickettsia spp. in the United States that causes a spotted fever rickettsiosis. To gain insights into its biology and pathogenesis, we applied the proteomics approach to establish a two-dimensional gel proteome reference map and combined this technique with cell surface biotinylation to identify surface-exposed proteins of a low-passage isolate of R. parkeri obtained from a patient. We identified 91 proteins by matrix-assisted laser desorption ionization-tandem time of flight mass spectrometry. Of these, 28 were characterized as surface proteins, including virulence-related proteins (e.g., outer membrane protein A [OmpA], OmpB, β-peptide, and RickA). Two-dimensional immunoblotting with serum from the R. parkeri-infected index patient was utilized to identify the immunoreactive proteins as potential targets for diagnosis and vaccine development. In addition to the known rickettsial antigens, OmpA and OmpB, we identified translation initiation factor 2, cell division protein FtsZ, and cysteinyl-tRNA synthetase as immunoreactive proteins. The proteome map with corresponding cell surface protein analysis and antigen detection will facilitate a better understanding of the mechanisms of rickettsial pathogenesis.

scholarly journals Susceptibility of Inbred Mice to Rickettsia parkeri

2012 ◽  
Vol 80 (5) ◽  
pp. 1846-1852 ◽  
Author(s):  
Britton J. Grasperge ◽  
Kathryn E. Reif ◽  
Timothy D. Morgan ◽  
Piyanate Sunyakumthorn ◽  
Joseph Bynog ◽  
...  
Keyword(s):  
Inbred Mice ◽  
Spotted Fever ◽  
Inbred Mouse ◽  
Transmission Model ◽  
Mouse Strains ◽  
Spotted Fever Group ◽  
Limited Information ◽  
Rickettsia Parkeri ◽  
Content Type ◽  
Boutonneuse Fever

ABSTRACTRickettsia parkeri, a member of the spotted fever groupRickettsia, is the causative agent of American boutonneuse fever in humans. Despite the increased recognition of human cases, limited information is available regarding the infection of invertebrate and vertebrate hosts for this emerging tick-borne disease. Toward the development of a viable transmission model and to further characterize the pathology associated withR. parkeriinfection, inbred mouse strains (A/J, BALB/c, C3H/HeJ, and C3H/HeN) were intravenously and intradermally inoculated with 105low-passage-numberR. parkeri(Portsmouth strain), and infection, gross pathology, and histopathology were scored. Additionally, a quantitative real-time PCR (qPCR) was performed to estimate rickettsial load in heart, lung, spleen, and liver tissues of infected mice at 19 days postinoculation. Of the A/J, BALB/c, and C3H/HeN mice, none displayed universal pathology consistent with sustained infection. Compared to age-matched control mice, the intravenously inoculated C3H/HeJ mice exhibited marked facial edema and marked splenomegaly upon gross examination, while the intradermally inoculated mice developed characteristic eschar-like lesions. The C3H/HeJ mice also exhibited the greatest concentrations of rickettsial DNA from heart, lung, liver, and spleen samples when examined by qPCR. The similarity of the pathology of human disease and sustained infection suggests that the C3H/HeJ strain of mice is a promising candidate for subsequent experiments to examine the tick transmission, dissemination, and pathology ofR. parkeririckettsiosis.

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

2020 ◽  
Author(s):  
Thomas P. Burke ◽  
Patrik Engström ◽  
Cuong J. Tran ◽  
Dustin R. Glasner ◽  
Diego A. Espinosa ◽  
...  
Keyword(s):  
Human Disease ◽  
Inbred Mice ◽  
Spotted Fever ◽  
Clinical Feature ◽  
Spotted Fever Group ◽  
Rickettsia Parkeri ◽  
Live Attenuated Vaccine ◽  
Interferon Receptor ◽  
Disseminated Disease ◽  
Deficient Mice

AbstractRickettsia are arthropod-borne pathogens that cause severe human disease worldwide. The spotted fever group (SFG) pathogen Rickettsia parkeri elicits skin lesion (eschar) formation in humans after tick bite. However, intradermal inoculation of inbred mice with millions of bacteria fails to elicit eschar formation or disseminated disease, hindering investigations into understanding eschar-associated rickettsiosis. Here, we report that intradermal infection of mice deficient for both interferon receptors (Ifnar-/-Ifngr-/-) with R. parkeri causes eschar formation, recapitulating the hallmark clinical feature of human disease. Intradermal infection with doses that recapitulate tick infestation caused eschar formation and lethality, including with as few as 10 bacteria. Using this model, we found that the actin-based motility protein Sca2 is required for R. parkeri dissemination from the skin to internal organs and for causing lethal disease, and that the abundant R. parkeri outer membrane protein OmpB contributes to eschar formation. We also found that immunizing mice with sca2 and ompB mutant R. parkeri protects against subsequent rechallenge with wild-type bacteria, revealing live-attenuated vaccine candidates. Thus, interferon receptor-deficient mice are a tractable model to investigate rickettsiosis, bacterial virulence factors, and immunity. Our results suggest that differences in interferon signaling in the skin between mice and humans may explain the discrepancy in susceptibility to SFG Rickettsia.

scholarly journals Serosurvey on rickettsiae of the spotted fever group and Rickettsia bellii among dogs in the state of Goiás, Brazil

2020 ◽  
Vol 29 (2) ◽  
Author(s):  
Lucianne Cardoso Neves ◽  
Ana Laura Gonçalves Barreto ◽  
Mariana Xavier de Souza ◽  
Danieli Brolo Martins ◽  
Amália Regina Mar Barbieri ◽  
...  
Keyword(s):  
Spotted Fever ◽  
First Record ◽  
Immunofluorescence Assay ◽  
The State ◽  
Spotted Fever Group ◽  
Serum Samples ◽  
Rickettsia Parkeri ◽  
Serological Tests ◽  
Rickettsia Rickettsii ◽  
Rickettsia Bellii

Abstract The purpose of this study was to do a serological survey on three rickettsial species: Rickettsia rickettsii and Rickettsia parkeri, two species of the spotted fever group (SFG) that are considered to be great importance for public health; and Rickettsia bellii, a species of unknown pathogenicity that infects a variety of human-biting ticks. Serum samples from 273 dogs were tested using the indirect immunofluorescence assay (IFA). A total of 52 samples (19.04%) were seropositive for at least one of the three Rickettsia spp. antigens. Thirty-eight (73.07%), twelve (23.07%) and one (1.92%) of these dogs showed homologous reactions to R. bellii, R. rickettsii and R. parkeri, respectively. Our results showed that the seroprevalence of Rickettsia spp. was relatively low. However, the positive serological tests indicated that these dogs had become infected by these agents at some point in their lives. Lastly, our study adds to the previous knowledge on the epidemiology of rickettsiosis in the state of Goiás by doing the first record of detection of anti-R. rickettsii, R. parkeri and R. bellii antibodies by IFA among dogs, thus indicating that these agents may be circulating in the dog population analyzed.

scholarly journals Serosurvey of Rickettsia spp. in cats from a Brazilian spotted fever-endemic area

2019 ◽  
Vol 28 (4) ◽  
pp. 713-721
Author(s):  
Juliana Cristina Rebonato Mendes ◽  
Louise Bach Kmetiuk ◽  
Camila Marinelli Martins ◽  
Aurea Maria Oliveira Canavessi ◽  
Tatiana Jimenez ◽  
...  
Keyword(s):  
Endemic Area ◽  
Spotted Fever ◽  
Rhipicephalus Sanguineus ◽  
Southeastern Brazil ◽  
Rickettsia Parkeri ◽  
Rickettsia Felis ◽  
Rickettsia Species ◽  
Brazilian Spotted Fever ◽  
Endemic Areas ◽  
The University

Abstract Rickettsia spp. bacteria are responsible for tick-borne diseases worldwide, mostly maintained by rickettsial amplifiers capybaras in Brazilian endemic areas. The campus of the University of São Paulo, in southeastern Brazil, is an area endemic for Brazilian spotted fever (BSF), with high density of capybaras and Amblyomma spp., along with confirmed human cases. Besides capybaras, the university has also an in-campus high population of sheltered and free-roaming cats. Accordingly, the aim of this study was to determine the prevalence and characteristics associated with Rickettsia rickettsii, Rickettsia parkeri and Rickettsia felis exposure among cats in a BSF-endemic area. Out of 51 cats sampled, 23/35 shelter (65.7%) and 5/16 free-roaming (31.2%) were positive (titers ≥ 64) for at least one Rickettsia species. Ticks species were present in 3/16 free-roaming cats (18.8%), consisting of Amblyomma spp., nymphs of Amblyomma sculptum and adult Rhipicephalus sanguineus sensu lato. Despite sharing the capybaras environment, the seropositivity among the free-roaming and shelter cats was lower than owned cats in other endemic areas. Whether equally or less exposed to rickettsial infection, compared with owned cats in endemic areas, free-roaming and shelter cats may be used as environmental sentinels for human exposure to rickettsiae in such areas.

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