Development of Tools for Conditional Knockouts in Chlamydia Chlamydia is an obligate intracellular bacterial pathogen that causes a range of serious diseases in humans. In developed countries, Chlamydia trachomatis is the primary cause of bacterial sexually transmitted infections (STI). In developing countries, C. trachomatis is not only a significant cause of STI, but it is also responsible for the primary cause of infectious preventable blindness, trachoma. The major concern of chlamydial infections is that they are often asymptomatic and undiagnosed, which can lead to chronic sequelae. These include pelvic inflammatory disease, tubal factor infertility, and reactive arthritis for C. trachomatis. Consequently, chlamydial diseases remain a significant burden on health care systems around the world. In adapting to obligate intracellular growth, Chlamydia has significantly reduced its genome size and eliminated genes from various pathways as it relies on the host cell for its metabolic needs. This, combined with its obligate intracellular dependence, makes Chlamydia a difficult organism with which to work and study. Recent development of genetic tools to study chlamydiae mechanistically have significantly enhanced our understanding of this pathogen. However, because most chlamydial genes are likely to be essential, the current toolset is insufficient to study these critical genes. We have demonstrated the feasibility of CRISPR interference to inducibly knock down chlamydial gene expression, in other words, to create conditional knockouts. The proposal is designed to leverage our early successes to better characterize and refine the utility of the system as well as to develop complementary strategies for blocking chlamydial protein function. Results will lead to the identification of novel diagnostic and therapeutic targets that have the potential to identify and treat asymptomatic chlamydial infections.

Public Health Relevance

Development of Tools for Conditional Knockouts in Chlamydia Chlamydiae are important pathogens of humans and significant causes of morbidity, causing a range of illnesses including sexually transmitted diseases, trachoma, pneumonia, and other respiratory tract infections. The burden of these infections stems from their lack of symptoms, which can lead to chronic conditions such as infertility, adult-onset asthma, and, in some cases, possibly exacerbating heart disease. The work proposed here is to further refine tools developed in the lab that will facilitate mechanistic studies of chlamydial biology, which in turn may lead to the identification of novel diagnostic or therapeutic targets that would potentially be able to identify and treat chronic chlamydial diseases.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1)
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Vincent, Leah Rebecca
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University of Nebraska Medical Center
Schools of Medicine
United States
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