scholarly journals The intracellular bacterium Rickettsia rickettsii exerts an inhibitory effect on the apoptosis of tick cells

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Larissa Almeida Martins ◽  
Giuseppe Palmisano ◽  
Mauro Cortez ◽  
Rebeca Kawahara ◽  
José Mario de Freitas Balanco ◽  
...  
Keyword(s):  
Bacterial Growth ◽  
Caspase 3 ◽  
Spotted Fever ◽  
Inhibitory Effect ◽  
Intracellular Bacterium ◽  
Mass Spectrometry Analysis ◽  
Dependent Manner ◽  
Label Free ◽  
Rocky Mountain Spotted Fever ◽  
Rickettsia Rickettsii

Abstract Background Rickettsia rickettsii is a tick-borne obligate intracellular bacterium that causes Rocky Mountain spotted fever, a life-threatening illness. To obtain an insight into the vector–pathogen interactions, we assessed the effects of infection with R. rickettsii on the proteome cells of the tick embryonic cell line BME26. Methods The proteome of BME26 cells was determined by label-free high-performance liquid chromatography coupled with tandem mass spectrometry analysis. Also evaluated were the effects of infection on the activity of caspase-3, assessed by the hydrolysis of a synthetic fluorogenic substrate in enzymatic assays, and on the exposition of phosphatidyserine, evaluated by live-cell fluorescence microscopy after labeling with annexin-V. Finally, the effects of activation or inhibition of caspase-3 activity on the growth of R. rickettsii in BME26 cells was determined. Results Tick proteins of different functional classes were modulated in a time-dependent manner by R. rickettsii infection. Regarding proteins involved in apoptosis, certain negative regulators were downregulated at the initial phase of the infection (6 h) but upregulated in the middle of the exponential phase of the bacterial growth (48 h). Microorganisms are known to be able to inhibit apoptosis of the host cell to ensure their survival and proliferation. We therefore evaluated the effects of infection on classic features of apoptotic cells and observed DNA fragmentation exclusively in noninfected cells. Moreover, both caspase-3 activity and phosphatidylserine exposition were lower in infected than in noninfected cells. Importantly, while the activation of caspase-3 exerted a detrimental effect on rickettsial proliferation, its inhibition increased bacterial growth. Conclusions Taken together, these results show that R. rickettsii modulates the proteome and exerts an inhibitory effect on apoptosis in tick cellsthat seems to be important to ensure cell colonization.

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 Comparative Genome Sequencing of Rickettsia rickettsii Strains That Differ in Virulence

2015 ◽  
Vol 83 (4) ◽  
pp. 1568-1576 ◽  
Author(s):  
Tina R. Clark ◽  
Nicholas F. Noriea ◽  
DeAnna C. Bublitz ◽  
Damon W. Ellison ◽  
Craig Martens ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Surface Antigen ◽  
Tandem Repeats ◽  
Spotted Fever ◽  
Protein A ◽  
Rocky Mountain Spotted Fever ◽  
Comparative Genome ◽  
Content Type ◽  
Rickettsia Rickettsii ◽  
Major Surface

Rickettsia rickettsiiis an obligate intracellular pathogen that is the causative agent of Rocky Mountain spotted fever. Strains ofR. rickettsiidiffer dramatically in virulence. In a guinea pig model of infection, the severity of disease as assessed by fever response varies from the most virulent, Sheila Smith, to Iowa, which causes no fever. To identify potential determinants of virulence inR. rickettsii, the genomes of two additional strains were sequenced for comparison to known sequences (comparative genome sequencing [CGS]).R. rickettsiiMorgan and R strains were compared to the avirulentR. rickettsiiIowa and virulentR. rickettsiiSheila Smith strains. The Montana strains Sheila Smith and R were found to be highly similar while the eastern strains Iowa and Morgan were most similar to each other. A major surface antigen, rickettsial outer membrane protein A (rOmpA), is severely truncated in the Iowa strain. The region ofompAcontaining 13 tandem repeats was sequenced, revealing only seven shared SNPs (four nonsynonymous) for R and Morgan strains compared to Sheila Smith, with an additional 17 SNPs identified in Morgan. Another major surface antigen and autotransporter, rOmpB, exhibits a defect in processing in the Iowa strain such that the beta fragment is not cleaved. Sequence analysis ofompBreveals identical sequences between Iowa and Morgan strains and between the R and Sheila Smith strains. The number of SNPs and insertions/deletions between sequences of the two Montana strains and the two eastern strains is low, thus narrowing the field of possible virulence factors.

scholarly journals Solution structure of the cold-shock-like protein fromRickettsia rickettsii

2012 ◽  
Vol 68 (11) ◽  
pp. 1284-1288 ◽  
Author(s):  
Kyle P. Gerarden ◽  
Andrew M. Fuchs ◽  
Jonathan M. Koch ◽  
Melissa M. Mueller ◽  
David R. Graupner ◽  
...  
Keyword(s):  
Solution Structure ◽  
Cold Shock ◽  
Spotted Fever ◽  
Rocky Mountain ◽  
Rocky Mountain Spotted Fever ◽  
Cold Shock Proteins ◽  
Rickettsia Rickettsii ◽  
The Family ◽  
Α Helix ◽  
Shock Proteins

Rocky Mountain spotted fever is caused byRickettsia rickettsiiinfection.R. rickettsiican be transmitted to mammals, including humans, through the bite of an infected hard-bodied tick of the family Ixodidae. Since theR. rickettsiigenome contains only one cold-shock-like protein and given the essential nature of cold-shock proteins in other bacteria, the structure of the cold-shock-like protein fromR. rickettsiiwas investigated. With the exception of a short α-helix found between β-strands 3 and 4, the solution structure of theR. rickettsiicold-shock-like protein has the typical Greek-key five-stranded β-barrel structure found in most cold-shock domains. Additionally, theR. rickettsiicold-shock-like protein, with a ΔGof unfolding of 18.4 kJ mol−1, has a similar stability when compared with other bacterial cold-shock proteins.

scholarly journals Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1527-1534 ◽  
Author(s):  
LA Sporn ◽  
PJ Haidaris ◽  
RJ Shi ◽  
Y Nemerson ◽  
DJ Silverman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tissue Factor ◽  
Thrombus Formation ◽  
Umbilical Vein ◽  
Spotted Fever ◽  
Clinical Manifestations ◽  
Mrna Levels ◽  
Rocky Mountain Spotted Fever ◽  
Rickettsia Rickettsii

Microvascular thrombi underlie many of the clinical manifestations of Rocky Mountain spotted fever (RMSF), a disease characterized by Rickettsia rickettsii infection of vascular endothelial cells. Studies were designed to determine whether R rickettsii-infection of cultured human umbilical vein endothelial cells results in tissue factor (TF) induction, a process that could directly activate coagulation in infected vessels. Whereas uninfected endothelial cell cultures showed essentially undetectable TF mRNA and activity, both TF mRNA and activity were present after R rickettsii infection. TF mRNA levels were transient, peaking at 4 hours after the initiation of infection, whereas the peak of TF activity occurred at 8 hours. Induction of the TF response requires the intracellular presence of R rickettsii organisms, because uninfected rickettsia were ineffective and the response was blocked by inhibiting rickettsial entry using cytochalasin B. TF induction was not mediated by endothelial cell release of soluble factor, because no response was induced using culture medium conditioned by R rickettsii-infected cells. Furthermore, preadsorption of suspensions of R rickettsii with polymyxin B to remove contaminating lipopolysaccharide did not eliminate the TF response. Induction of TF in vital endothelial cells during R rickettsii infection could be the trigger for vascular thrombus formation of RMSF.

scholarly journals Prednisolone at anti-inflammatory or immunosuppressive dosages in conjunction with doxycycline does not potentiate the severity of Rickettsia rickettsii infection in dogs.

1997 ◽  
Vol 41 (1) ◽  
pp. 141-147 ◽  
Author(s):  
E B Breitschwerdt ◽  
M G Davidson ◽  
B C Hegarty ◽  
M G Papich ◽  
C B Grindem
Keyword(s):  
Spotted Fever ◽  
Rocky Mountain ◽  
Rocky Mountain Spotted Fever ◽  
Serum Samples ◽  
Concurrent Administration ◽  
Rickettsia Rickettsii ◽  
Beneficial Effects ◽  
Concurrent Use ◽  
Antibody Titers ◽  
Anti Inflammatory

Dogs were experimentally inoculated with Rickettsia rickettsii to determine if anti-inflammatory or immunosuppressive dosages of prednisolone, when administered in conjunction with an antirickettsial antibiotic (doxycycline), induced therapeutically relevant pathophysiological consequences that ultimately influence disease outcome. Although the duration of rickettsemia was prolonged in dogs receiving immunosuppressive, but not anti-inflammatory, corticosteroids, concurrent administration of doxycycline and corticosteroids conferred no other detected detrimental effects. Treatment with doxycycline or doxycycline in conjunction with prednisolone resulted in decreased R. rickettsii-specific antibody titers; however, examination of appropriately timed acute- and convalescent-phase serum samples would have facilitated an accurate diagnosis of Rocky Mountain spotted fever (RMSF) in all 16 dogs. We conclude that the concurrent use of anti-inflammatory or immunosuppressive doses of prednisolone in conjunction with doxycycline, early in the course of experimental RMSF, confers no clinically relevant detrimental effects and that additional studies might be indicated to detect possible beneficial effects in cases of severe or potentially fulminant RMSF. However, because the illness induced in these dogs was of mild to moderate severity, the results of this study should definitely not be construed as supporting the safety or efficacy of prednisolone for treatment of severe canine or human RMSF.

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