Chlamydia trachomatis represents a significant health concern in the United States. A substantial burden exists due to the prevalence and the combined health and socioeconomic impact of acute and chronic disease. Chlamydiae are obligate intracellular parasites that undergo a complex developmental cycle. All Chlamydia species express a type III secretion system (T3SS), and based on analogy with other T3SS-expressing pathogens, this mechanism likely contributes significantly to overall pathogenesis. Although definitive association of T3S with chlamydial virulence has proven difficult, the newly-acquired ability to genetically manipulate chlamydiae has opened new doors for progress. We present preliminary data describing the first ever Chlamydia-specific suicide vector and propose to leverage this new approach to target T3SS genes for inactivation. Specifically we will further develop the suicide vector system and directly create null mutations in specific T3S effector genes. We also propose approaches to conditionally inactivate T3S capability. At the end of these studies, we will have established molecular tools that will benefit the entire Chlamydia research community. In addition, we will gain a better understanding of how the T3SS contributes to chlamydial virulence.
Sexually transmitted disease remains a significant health burden world-wide and infections with Chlamydia trachomatis are common. We have developed a novel method to generate null mutations in chlamydial genes and will leverage this approach to gauge the importance of selected type III secretion proteins in chlamydial pathogenesis.
| Rahnama, Mostafa; Fields, Kenneth A (2018) Transformation of Chlamydia: current approaches and impact on our understanding of chlamydial infection biology. Microbes Infect 20:445-450 |
| Keb, G; Hayman, R; Fields, K A (2018) Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion in Chlamydia trachomatis and Can Reverse Cassette-Induced Polar Effects. J Bacteriol 200: |
| Mueller, Konrad E; Wolf, Katerina; Fields, Kenneth A (2017) Chlamydia trachomatis Transformation and Allelic Exchange Mutagenesis. Curr Protoc Microbiol 45:11A.3.1-11A.3.15 |
