Rock Mountain Spotted Fever, known in Brazil as Brazilian Spotted Fever (BSF), is the most severe rickettsiosis that affects humans. In Brazil, the etiologic agent of this disease, the obligate intracellular bacterium Rickettsia rickettsii, is transmitted by bite of ticks from the genera Amblyomma. Besides the low prevalence of infected ticks from BSF endemic areas, experimentally infected ticks present lower reproductive and survival rates. These data suggest that the bacterium is also detrimental to its vector ticks. Therefore, the central aim of my research group is elucidate the molecular mechanisms of the interactions between R. rickettsii and ticks. To that end, we use different methods and approaches. Firstly, we analyzed the effects of infection on the gene expression profile of ticks by suppressive subtractive hybridization (SSH). More recently, we also evaluated the genes of tick midgut that are modulated by infection using high-throughput RNA sequencing (RNAseq). The function of the protein products of modulated genes, including antimicrobial peptides, Kunitz-type domain containing proteins, and secreted proteins, has been characterized by interference RNA (RNAi). We also stated investigating the proteins and lipids that are differentially secreted in tick saliva by mass spectrometry (MS). Another main aim of my research group is to determine the molecular pathogenic mechanisms of R. rickettsii against ticks. Therefore, we determined the global gene expression profile of this bacterium exposed to a temperature upshift and blood feeding. Both environmental stimuli had been previously enrolled as important factors for reactivation of bacterial virulence within ticks, but the molecular mechanisms have not been completely elucidated. Using oligonucleotide microarrays, we observed that blood feeding modulate five times more genes than temperature upshift. Among genes induced by blood feeding, some code virulence factors, such as components of type IV secretion system (T4SS). T4SS is used by intracellular bacteria to translocate molecules (effectors) to the cytoplasm of host cells. We are currently identifying the effectors of R. rickettsii by in silico analysis coupled to protein-protein interaction assays. In addition, we are analyzing the set of secreted proteins (secretome) of R. rickettsii by MS.