Comparative transcriptomics in vector-rickettsiae interactions:New insights into molecular interactions between Rickettsia typhi and its insect vector
AdvisorAzad, Abdu F.
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AbstractRickettsia typhi is an obligate intracellular bacterium, and the causative agent of murine typhus, a flea-borne febrile illness prevalent and endemic in coastal areas throughout the world. Unlike most vector-borne pathogens, rickettsiae have the unique ability to persist in their vector host. Thus, once the infection is established, infected arthropods may serve as reservoirs of rickettsiae in nature. The goal of this study was to examine global transcription profiles of both R. typhi and its flea vector, Ctenocephalides felis, to elucidate molecular patterns underlying the tight associations between the two organisms. We hypothesize that in order to establish a persistent infection, specific changes in gene expression of both R. typhi and its flea vector, C. felis, are elicited in response to each other. This intricate molecular balancing act likely involves R. typhi-directed events to allow for successful infection of the flea midgut, as well as concomitant flea responses to limit the infection. Microarray analysis was used to uncover differences in global transcription profiles of R. typhi in response to a down-shift in temperature in vitro, mimicking one of the environmental changes encountered by R. typhi as it transitions from the mammalian host to the flea vector. This study identified differential transcription of genes from various functional groups, including genes that encode a putative rickettsial type IV secretion system, as well as upregulation of a rickettsial gene encoding a hypothetical protein (RT0279). Transcriptional analysis indicates that RT0279 is co-transcribed with downstream rickettsial vir-homologs, and when expressed in E. coli, is secreted into the extracellular milieu. Additionally, these studies compared the global transcription profiles of R. typhi infected and uninfected C.felis midguts to identify candidate flea midgut genes involved in the flea response to R. typhi infection. Follow up studies identified significant differences in gene expression of putative C. felis proteases and GTPases over an infection time course in vivo.
DescriptionUniversity of Maryland in Baltimore. Molecular Microbiology and Immunology. Ph.D. 2009