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Our laboratory focuses on three main areas of chlamydial research. First, we investigate the mechanisms used by chlamydiae to develop and maintain their intracellular environment (the inclusion) within infected cells. We (and others) have identified a collection of proteins- termed Inc proteins- that are localized to the inclusion membrane. These proteins contact the cytosol in the infected cell and are positioned to directly interact with host cell proteins. Continued studies in this area will further our understanding of the cellular processes parasitized by chlamydiae, and may identify ways to interfere with this parasitism.
Second, we conduct genomics analyses of clinical C. trachomatis isolates. There is no system for the genetic manipulation of Chlamydia, and thus, the analysis of individual genes within this system is challenging. We approach this problem through the study of a large library of clinical isolates assembled by collaborators at the University of Washington. We have identified strains within this library that have unique properties in vitro and in vivo, and we are currently using a genomics approach to investigate these unusual strains. Our approach has thus far been successful in associating IncA with a nonfusogenic phenotype, and in the identification of a unique property of secondary inclusion formation by some strains.
Finally, we investigate antibiotic resistance in Chlamydia suis, a pathogen of importance to the swine industry. We demonstrated that many C. suis strains are stably tetracycline resistant, and that this resistance is mediated via a TetC efflux pump found in many other bacteria. This is significant because tetracycline is a frontline drug of choice in treatment of both human and veterinary chlamydial infections, and widespread resistance would be a serious problem. This is also the first example of any horizontally acquired antibiotic resistance gene in any chlamydial species. We continue to explore the distribution of the resistance phenotype, the mechanism of acquisition of the resistance genes by C. suis, and the possible use of the resistance gene as a marker for stable transformation of chlamydiae.