Dissertation/Thesis Abstract

The Host-Pathogen Relationship in Rickettsia: Epidemiological Analysis of RMSF in Ohio and a Comparative Molecular Analysis of Four VIR Genes
by Carmichael, Jennifer R., Ph.D., The Ohio State University, 2008, 206; 10630855
Abstract (Summary)

Members of the vector-borne bacterial genus Rickettsia represent an emerging infectious disease threat and have continually been implicated in epidemics worldwide. It is of vital importance to understand the geographical distribution of disease and rickettsial-infected arthropods vectors. In addition, understanding the dynamics of the relationship between rickettsiae and their arthropod hosts will help aid in identifying important factors for virulence. Dermacentor variabilis dog ticks are the main vector in the eastern United States for Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever. The frequency of rickettsial-infected ticks and their geographical location in Ohio over the last twenty years was analyzed. The frequency of rickettsial species was found to remain relatively constant (about 20%), but the incidence of R. rickettsii has increased from 6 to 16%. Also, the geographic distribution of rickettsial-positive ticks has expanded, corresponding to a rise of RMSF in these new areas. Type IV secretion system genes, like the vir group, are important for pathogenicity in many pathogens, but have not been analyzed in Rickettsia. Four vir genes, virB8, virB11, virB4, and virD4 were analyzed in Rickettsia amblyommii infected Amblyomma americanum Lone Star ticks from across the Northeast United States. Results showed that important protein motifs are mutated or absent. This evidence suggests the vir genes may not be functional in Rickettsia or they have evolved a novel role. In addition, analysis of virD4 showed that isolates were most similar to Rickettsia conorii and R. rickettsii, two highly pathogenic species. To determine if these genes are important for virulence, a novel qPCR approach was designed to compare the RNA expression in R. amblyommii-infected A. americanum tick and Vero cells. Here, expression of virB8 and virD4 was increased in Vero cells, while virB4 and virB11 had decreased expression. Since rickettsiae cause disease in humans, increases in expression levels in the mammalian Vero cells may be important for pathogenicity. Understanding all levels of disease, from basic biology and epidemiology, analysis of potential virulence genes, and functional analysis via RNA expression, contributes information that leads us closer to determining the process of rickettsial pathogenicity.

Indexing (document details)
Advisor: Fuerst, Paul
Commitee: Burghes, Arthur, Leone, Gustavo, Needham, Glen
School: The Ohio State University
Department: Molecular Genetics
School Location: United States -- Ohio
Source: DAI-B 78/11(E), Dissertation Abstracts International
Subjects: Molecular biology
Keywords: Amblyomma, Dermacentor, Host-pathogen, Rickettsia, Ticks, Vir gene
Publication Number: 10630855
ISBN: 9780355011869
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