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Isolate-Dependent Differences in Clinical, Pathological, and Transcriptional Profiles following In Vitro and In Vivo Infections with Rickettsia rickettsii

Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever (RMSF), a life-threatening tick-borne disease that affects humans and various animal species, has been recognized in medicine and science for more than 100 years. Isolate-dependent differences in virulence of R. rickettsii...

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Autores principales: Galletti, Maria F. B. M., Paddock, Christopher D., Hecht, Joy A., Biggerstaff, Brad J., Ritter, Jana M., Karpathy, Sandor E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090960/
https://www.ncbi.nlm.nih.gov/pubmed/33495273
http://dx.doi.org/10.1128/IAI.00626-20
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author Galletti, Maria F. B. M.
Paddock, Christopher D.
Hecht, Joy A.
Biggerstaff, Brad J.
Ritter, Jana M.
Karpathy, Sandor E.
author_facet Galletti, Maria F. B. M.
Paddock, Christopher D.
Hecht, Joy A.
Biggerstaff, Brad J.
Ritter, Jana M.
Karpathy, Sandor E.
author_sort Galletti, Maria F. B. M.
collection PubMed
description Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever (RMSF), a life-threatening tick-borne disease that affects humans and various animal species, has been recognized in medicine and science for more than 100 years. Isolate-dependent differences in virulence of R. rickettsii have been documented for many decades; nonetheless, the specific genetic and phenotypic factors responsible for these differences have not been characterized. Using in vivo and in vitro methods, we identified multiple phenotypic differences among six geographically distinct isolates of R. rickettsii, representing isolates from the United States, Costa Rica, and Brazil. Aggregate phenotypic data, derived from growth in Vero E6 cells and from clinical and pathological characteristics following infection of male guinea pigs (Cavia porcellus), allowed separation of these isolates into three categories: nonvirulent (Iowa), mildly virulent (Sawtooth and Gila), and highly virulent (Sheila Smith(T), Costa Rica, and Taiaçu). Transcriptional profiles of 11 recognized or putative virulence factors confirmed the isolate-dependent differences between mildly and highly virulent isolates. These data corroborate previous qualitative assessments of strain virulence and suggest further that a critical and previously underappreciated balance between bacterial growth and host immune response could leverage strain pathogenicity. Also, this work provides insight into isolate-specific microbiological factors that contribute to the outcome of RMSF and confirms the hypothesis that distinct rickettsial isolates also differ phenotypically, which could influence the severity of disease in vertebrate hosts.
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spelling pubmed-80909602021-05-11 Isolate-Dependent Differences in Clinical, Pathological, and Transcriptional Profiles following In Vitro and In Vivo Infections with Rickettsia rickettsii Galletti, Maria F. B. M. Paddock, Christopher D. Hecht, Joy A. Biggerstaff, Brad J. Ritter, Jana M. Karpathy, Sandor E. Infect Immun Bacterial Infections Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever (RMSF), a life-threatening tick-borne disease that affects humans and various animal species, has been recognized in medicine and science for more than 100 years. Isolate-dependent differences in virulence of R. rickettsii have been documented for many decades; nonetheless, the specific genetic and phenotypic factors responsible for these differences have not been characterized. Using in vivo and in vitro methods, we identified multiple phenotypic differences among six geographically distinct isolates of R. rickettsii, representing isolates from the United States, Costa Rica, and Brazil. Aggregate phenotypic data, derived from growth in Vero E6 cells and from clinical and pathological characteristics following infection of male guinea pigs (Cavia porcellus), allowed separation of these isolates into three categories: nonvirulent (Iowa), mildly virulent (Sawtooth and Gila), and highly virulent (Sheila Smith(T), Costa Rica, and Taiaçu). Transcriptional profiles of 11 recognized or putative virulence factors confirmed the isolate-dependent differences between mildly and highly virulent isolates. These data corroborate previous qualitative assessments of strain virulence and suggest further that a critical and previously underappreciated balance between bacterial growth and host immune response could leverage strain pathogenicity. Also, this work provides insight into isolate-specific microbiological factors that contribute to the outcome of RMSF and confirms the hypothesis that distinct rickettsial isolates also differ phenotypically, which could influence the severity of disease in vertebrate hosts. American Society for Microbiology 2021-03-17 /pmc/articles/PMC8090960/ /pubmed/33495273 http://dx.doi.org/10.1128/IAI.00626-20 Text en https://doi.org/10.1128/AuthorWarrantyLicense.v1This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.
spellingShingle Bacterial Infections
Galletti, Maria F. B. M.
Paddock, Christopher D.
Hecht, Joy A.
Biggerstaff, Brad J.
Ritter, Jana M.
Karpathy, Sandor E.
Isolate-Dependent Differences in Clinical, Pathological, and Transcriptional Profiles following In Vitro and In Vivo Infections with Rickettsia rickettsii
title Isolate-Dependent Differences in Clinical, Pathological, and Transcriptional Profiles following In Vitro and In Vivo Infections with Rickettsia rickettsii
title_full Isolate-Dependent Differences in Clinical, Pathological, and Transcriptional Profiles following In Vitro and In Vivo Infections with Rickettsia rickettsii
title_fullStr Isolate-Dependent Differences in Clinical, Pathological, and Transcriptional Profiles following In Vitro and In Vivo Infections with Rickettsia rickettsii
title_full_unstemmed Isolate-Dependent Differences in Clinical, Pathological, and Transcriptional Profiles following In Vitro and In Vivo Infections with Rickettsia rickettsii
title_short Isolate-Dependent Differences in Clinical, Pathological, and Transcriptional Profiles following In Vitro and In Vivo Infections with Rickettsia rickettsii
title_sort isolate-dependent differences in clinical, pathological, and transcriptional profiles following in vitro and in vivo infections with rickettsia rickettsii
topic Bacterial Infections
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090960/
https://www.ncbi.nlm.nih.gov/pubmed/33495273
http://dx.doi.org/10.1128/IAI.00626-20
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