scholarly journals A Kunitz Protease Inhibitor fromDermacentor variabilis, a Vector for Spotted Fever Group Rickettsiae, LimitsRickettsia montanensisInvasion

2010 ◽  
Vol 79 (1) ◽  
pp. 321-329 ◽  
Author(s):  
Shane M. Ceraul ◽  
Ashley Chung ◽  
Khandra T. Sears ◽  
Vsevolod L. Popov ◽  
Magda Beier-Sexton ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Host Cell ◽  
Spotted Fever ◽  
Dermacentor Variabilis ◽  
Spotted Fever Group ◽  
Kunitz Protease Inhibitor ◽  
Dog Tick ◽  
Interfering Rna ◽  
Tick Midgut

ABSTRACTA defining facet of tick-Rickettsiasymbioses is the molecular strategy employed by each partner to ensure its own survival. Ticks must control rickettsial colonization to avoid immediate death. In the current study, we show that rickettsial abundance in the tick midgut increases once the expression of a Kunitz-type serine protease inhibitor from the American dog tick (Dermacentor variabilis) (DvKPI) is suppressed by small interfering RNA (siRNA). A series ofin vitroinvasion assays suggested that DvKPI limits rickettsial colonization during host cell entry. Interestingly, we observed that DvKPI associates with rickettsiaein vitroas well as in the tick midgut. Collectively, our data demonstrate that DvKPI limits host cell invasion byRickettsia montanensis, possibly through an association with the bacterium.

scholarly journals Exploring the niche of Rickettsia montanensis (Rickettsiales: Rickettsiaceae) infection of the American dog tick (Acari: Ixodidae), using multiple species distribution model approaches.

2020 ◽  
Author(s):  
Catherine Lippi ◽  
Holly D Gaff ◽  
Alexis L White ◽  
Heidi K St John ◽  
Allen L Richards ◽  
...  
Keyword(s):  
Species Distribution ◽  
Species Distribution Model ◽  
Health Planning ◽  
Spotted Fever ◽  
Dermacentor Variabilis ◽  
Distribution Model ◽  
Spotted Fever Group ◽  
Modeling Framework ◽  
American Dog Tick ◽  
Dog Tick

The American dog tick, Dermacentor variabilis (Say), is a vector for several human disease causing pathogens such as tularemia, Rocky Mountain spotted fever, and the understudied spotted fever group rickettsiae (SFGR) infection caused by Rickettsia montanensis. It is important for public health planning and intervention to understand the distribution of this tick and pathogen encounter risk. Risk is often described in terms of vector distribution, but greatest risk may be concentrated where more vectors are positive for a given pathogen. When assessing species distributions, the choice of modeling framework and spatial layers used to make predictions are important. We first updated the modeled distribution of D. variabilis and R. montanensis using MaxEnt, refining bioclimatic data inputs, and including soils variables. We then compared geospatial predictions from five species distribution modeling (SDM) frameworks. In contrast to previous work, we additionally assessed whether the R. montanensis positive D. variabilis distribution is nested within a larger overall D. variabilis distribution, representing a fitness cost hypothesis. We found that 1) adding soils layers improved the accuracy of the MaxEnt model; 2) the predicted "infected niche" was smaller than the overall predicted niche across all models; and 3) each model predicted different sizes of suitable niche, at different levels of probability. Importantly, the models were not directly comparable in output style, which could create confusion in interpretation when developing planning tools. The random forest (RF) model had the best measured validity and fit, suggesting it may be most appropriate to these data.

scholarly journals Identification of Host Proteins Involved in Rickettsial Invasion of Tick Cells

2014 ◽  
Vol 83 (3) ◽  
pp. 1048-1055 ◽  
Author(s):  
Natthida Petchampai ◽  
Piyanate Sunyakumthorn ◽  
Kaikhushroo H. Banajee ◽  
Victoria I. Verhoeve ◽  
Michael T. Kearney ◽  
...  
Keyword(s):  
Host Cell ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Rho Gtpase ◽  
Spotted Fever ◽  
Dermacentor Variabilis ◽  
Host Cells ◽  
Spotted Fever Group ◽  
Bacterial Survival ◽  
Content Type

Tick-borne spotted fever group (SFG)Rickettsiaspecies are obligate intracellular bacteria capable of infecting both vertebrate and invertebrate host cells, an essential process for subsequent bacterial survival in distinct hosts. The host cell signaling molecules involved in the uptake ofRickettsiainto mammalian andDrosophilacells have been identified; however, invasion into tick cells is understudied. Considering the movement of SFGRickettsiabetween vertebrate and invertebrate hosts, the hypothesis is that conserved mechanisms are utilized for host cell invasion. The current study employed biochemical inhibition assays to determine the tick proteins involved inRickettsia montanensisinfection of tick-derived cells from a natural host,Dermacentor variabilis. The results revealed several tick proteins important for rickettsial invasion, including actin filaments, actin-related protein 2/3 complex, phosphatidylinositol-3′-kinase, protein tyrosine kinases (PTKs), Src family PTK, focal adhesion kinase, Rho GTPase Rac1, and neural Wiskott-Aldrich syndrome protein. Delineating the molecular mechanisms of rickettsial infection is critical to a thorough understanding of rickettsial transmission in tick populations and the ecology of tick-borne rickettsial diseases.

scholarly journals Exploring the Niche of Rickettsia montanensis (Rickettsiales: Rickettsiaceae) Infection of the American Dog Tick (Acari: Ixodidae), Using Multiple Species Distribution Model Approaches

2020 ◽  
Author(s):  
Catherine A Lippi ◽  
Holly D Gaff ◽  
Alexis L White ◽  
Heidi K St. John ◽  
Allen L Richards ◽  
...  
Keyword(s):  
Species Distribution ◽  
Species Distribution Model ◽  
Health Planning ◽  
Spotted Fever ◽  
Dermacentor Variabilis ◽  
Distribution Model ◽  
Spotted Fever Group ◽  
Modeling Framework ◽  
American Dog Tick ◽  
Dog Tick

Abstract The American dog tick, Dermacentor variabilis (Say) (Acari: Ixodidae), is a vector for several human disease-causing pathogens such as tularemia, Rocky Mountain spotted fever, and the understudied spotted fever group rickettsiae (SFGR) infection caused by Rickettsia montanensis. It is important for public health planning and intervention to understand the distribution of this tick and pathogen encounter risk. Risk is often described in terms of vector distribution, but greatest risk may be concentrated where more vectors are positive for a given pathogen. When assessing species distributions, the choice of modeling framework and spatial layers used to make predictions are important. We first updated the modeled distribution of D. variabilis and R. montanensis using maximum entropy (MaxEnt), refining bioclimatic data inputs, and including soil variables. We then compared geospatial predictions from five species distribution modeling frameworks. In contrast to previous work, we additionally assessed whether the R. montanensis positive D. variabilis distribution is nested within a larger overall D. variabilis distribution, representing a fitness cost hypothesis. We found that 1) adding soil layers improved the accuracy of the MaxEnt model; 2) the predicted ‘infected niche’ was smaller than the overall predicted niche across all models; and 3) each model predicted different sizes of suitable niche, at different levels of probability. Importantly, the models were not directly comparable in output style, which could create confusion in interpretation when developing planning tools. The random forest (RF) model had the best measured validity and fit, suggesting it may be most appropriate to these data.

Collaborating With Community Scientists Across Arkansas to Update Tick Distributions and Pathogen Prevalence of Spotted Fever Group Rickettsia and Ehrlichia

2021 ◽  
Author(s):  
Ashley P G Dowling ◽  
Sean G Young ◽  
Kelly Loftin
Keyword(s):  
Tick Species ◽  
Spotted Fever ◽  
Dermacentor Variabilis ◽  
Amblyomma Americanum ◽  
Spotted Fever Group ◽  
Primary Role ◽  
Prevalence Rates ◽  
Spotted Fever Group Rickettsia ◽  
Community Science ◽  
Tick Distributions

Abstract Tick-borne diseases (TBD) in humans have dramatically increased over recent years and although the bulk of cases are attributable to Lyme Disease in the Northeastern US, TBDs like spotted fever rickettsiosis and ehrlichiosis heavily impact other parts of the country, namely the mid-south. Understanding tick and pathogen distributions and prevalence traditionally requires active surveillance, which quickly becomes logistically and financially unrealistic as the geographic area of focus increases. We report on a community science effort to survey ticks across Arkansas to obtain updated data on tick distributions and prevalence of human tick-borne disease-causing pathogens in the most commonly encountered ticks. During a 20-mo period, Arkansans submitted 9,002 ticks from 71 of the 75 counties in the state. Amblyomma americanum was the most common tick species received, accounting for 76% of total tick submissions. Nearly 6,000 samples were screened for spotted fever group Rickettsia (SFGR) and Ehrlichia, resulting in general prevalence rates of 37.4 and 5.1%, respectively. In addition, 145 ticks (2.5%) were infected with both SFGR and Ehrlichia. Arkansas Department of Health reported 2,281 spotted fever and 380 ehrlichiosis cases during the same period as our tick collections. Since known SFGR vectors Dermacentor variabilis and Amblyomma maculatum were not the most common ticks submitted, nor did they have the highest prevalence rates of SFGR, it appears that other tick species play the primary role in infecting humans with SFGR. Our investigation demonstrated the utility of community science to efficiently and economically survey ticks and identify vector-borne disease risk in Arkansas.

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.

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.

scholarly journals Minimal Duration of Tick Attachment Sufficient for Transmission of Infectious Rickettsia rickettsii (Rickettsiales: Rickettsiaceae) by Its Primary Vector Dermacentor variabilis (Acari: Ixodidae): Duration of Rickettsial Reactivation in the Vector Revisited

2019 ◽  
Author(s):  
Michael L Levin ◽  
Shelby L Ford ◽  
Kris Hartzer ◽  
Lnna Krapiunaya ◽  
Hannah Stanley ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Guinea Pigs ◽  
Pathogenic Bacteria ◽  
Spotted Fever ◽  
Dermacentor Variabilis ◽  
Control Group ◽  
Spotted Fever Group ◽  
Susceptible Host ◽  
Rickettsia Rickettsii ◽  
Tick Attachment

Abstract It has been reported that starving ticks do not transmit spotted fever group Rickettsia immediately upon attachment because pathogenic bacteria exist in a dormant, uninfectious state and require time for ‘reactivation’ before transmission to a susceptible host. To clarify the length of reactivation period, we exposed guinea pigs to bites of Rickettsia rickettsii-infected Dermacentor variabilis (Say) and allowed ticks to remain attached for predetermined time periods from 0 to 48 h. Following removal of attached ticks, salivary glands were immediately tested by PCR, while guinea pigs were observed for 10–12 d post-exposure. Guinea pigs in a control group were subcutaneously inoculated with salivary glands from unfed D. variabilis from the same cohort. In a parallel experiment, skin at the location of tick bite was also excised at the time of tick removal to ascertain dissemination of pathogen from the inoculation site. Animals in every exposure group developed clinical and pathological signs of infection. The severity of rickettsial infection in animals increased with the length of tick attachment, but even attachments for less than 8 h resulted in clinically identifiable infection in some guinea pigs. Guinea pigs inoculated with salivary glands from unfed ticks also became severely ill. Results of our study indicate that R. rickettsii residing in salivary glands of unfed questing ticks does not necessarily require a period of reactivation to precede the salivary transmission and ticks can transmit infectious Rickettsia virtually as soon as they attach to the host.

scholarly journals Targeted Disruption of Toxoplasma gondii Serine Protease Inhibitor 1 Increases Bradyzoite Cyst FormationIn Vitroand Parasite Tissue Burden in Mice

2011 ◽  
Vol 80 (3) ◽  
pp. 1156-1165 ◽  
Author(s):  
Viviana Pszenny ◽  
Paul H. Davis ◽  
Xing W. Zhou ◽  
Christopher A. Hunter ◽  
Vern B. Carruthers ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Protease Inhibitor ◽  
Host Cell ◽  
Serine Protease ◽  
Parasitophorous Vacuole ◽  
Parasite Burden ◽  
Serine Protease Inhibitor ◽  
Genomic Locus ◽  
Content Type

As an intracellular protozoan parasite,Toxoplasma gondiiis likely to exploit proteases for host cell invasion, acquisition of nutrients, avoidance of host protective responses, escape from the parasitophorous vacuole, differentiation, and other activities.T. gondiiserine protease inhibitor 1 (TgPI1) is the most abundantly expressed protease inhibitor in parasite tachyzoites. We show here that alternative splicing produces twoTgPI1 isoforms, both of which are secreted via dense granules into the parasitophorous vacuole shortly after invasion, become progressively more abundant over the course of the infectious cycle, and can be detected in the infected host cell cytoplasm. To investigateTgPI1 function, the endogenous genomic locus was disrupted in the RH strain background. ΔTgPI1 parasites replicate normally as tachyzoites but exhibit increased bradyzoite gene transcription and labeling of vacuoles withDolichos bifloruslectin under conditions promotingin vitrodifferentiation. The differentiation phenotype can be partially complemented by eitherTgPI1 isoform. Mice infected with the ΔTgPI1 mutant display ∼3-fold-increased parasite burden in the spleen and liver, and thisin vivophenotype is also complemented by eitherTgPI1 isoform. These results demonstrate thatTgPI1 influences both parasite virulence and bradyzoite differentiation, presumably by inhibiting parasite and/or host serine proteases.

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