Nitric Oxide Inhibition of Rickettsia rickettsii

2021 ◽  
Author(s):  
Liam Fitzsimmons ◽  
Tina Clark ◽  
Ted Hackstadt
Keyword(s):  
Nitric Oxide ◽  
Innate Immunity ◽  
Pathogenic Bacteria ◽  
Spotted Fever ◽  
Bacterial Pathogen ◽  
Rocky Mountain ◽  
Cell Types ◽  
Host Cells ◽  
Rocky Mountain Spotted Fever ◽  
Rickettsia Rickettsii

Rickettsia rickettsii , the causative agent of Rocky Mountain spotted fever, is an enzootic, obligate intracellular bacterial pathogen. Nitric oxide (NO) synthesized by the inducible nitric oxide synthase (iNOS) is a potent antimicrobial component of innate immunity and has been implicated in the control of virulent Rickettsia spp. in diverse cell types. In this study, we examined the antibacterial role of NO on R. rickettsii . Our results indicate that NO challenge dramatically reduces R. rickettsii adhesion through the disruption of bacterial energetics. Additionally, NO-treated R. rickettsii were unable to synthesize protein or replicate in permissive cells. Activated, NO-producing macrophages restricted R. rickettsii infections, but inhibition of iNOS ablated the inhibition of bacterial growth. These data indicate that NO is a potent anti-rickettsial effector of innate immunity that targets energy generation in these pathogenic bacteria to prevent growth and subversion of infected host cells.

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 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 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.

Rickettsia rickettsii (Rocky Mountain Spotted Fever)

2008 ◽  
pp. 915-919 ◽  
Author(s):  
Christopher D. Paddock ◽  
Marta A. Guerra ◽  
James E. Childs ◽  
David L. Swerdlow
Keyword(s):  
Spotted Fever ◽  
Rocky Mountain ◽  
Rocky Mountain Spotted Fever ◽  
Rickettsia Rickettsii

scholarly journals Molecular and Functional Analysis of the lepB Gene, Encoding a Type I Signal Peptidase from Rickettsia rickettsii and Rickettsia typhi

2003 ◽  
Vol 185 (15) ◽  
pp. 4578-4584 ◽  
Author(s):  
M. Sayeedur Rahman ◽  
Jason A. Simser ◽  
Kevin R. Macaluso ◽  
Abdu F. Azad
Keyword(s):  
Spotted Fever ◽  
Rocky Mountain ◽  
Amino Acid Sequences ◽  
Signal Peptidase ◽  
Type I ◽  
Rocky Mountain Spotted Fever ◽  
Rickettsia Typhi ◽  
Rickettsia Rickettsii ◽  
Signal Peptidase I

ABSTRACT The type I signal peptidase lepB genes from Rickettsia rickettsii and Rickettsia typhi, the etiologic agents of Rocky Mountain spotted fever and murine typhus, respectively, were cloned and characterized. Sequence analysis of the cloned lepB genes from R. rickettsii and R. typhi shows open reading frames of 801 and 795 nucleotides, respectively. Alignment analysis of the deduced amino acid sequences reveals the presence of highly conserved motifs that are important for the catalytic activity of bacterial type I signal peptidase. Reverse transcription-PCR and Northern blot analysis demonstrated that the lepB gene of R. rickettsii is cotranscribed in a polycistronic message with the putative nuoF (encoding NADH dehydrogenase I chain F), secF (encoding protein export membrane protein), and rnc (encoding RNase III) genes in a secF-nuoF-lepB-rnc cluster. The cloned lepB genes from R. rickettsii and R. typhi have been demonstrated to possess signal peptidase I activity in Escherichia coli preprotein processing in vivo by complementation assay.

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