Intracellular bacterial pathogens are a diverse group of bacteria with an acutely adapted life cycle. These bacteria enter and exploit the intracellular environment of a eukaryotic host cell for replication and survival. The study of this class of pathogens is uniquely challenging as these organisms are dependent on the host cell for many aspects of their life cycle. Gaining access to and utilizing the resources of the host cell depends on a complex interaction between the host and pathogen. Throughout my career my research interests have focused on the intimate interaction between host cells and these pathogens. Although I have contributed to the understanding of pathogenesis in both Coxiella burnetii and Rickettsia species, my current work focuses on the pathogenesis of Chlamydia.
Chlamydiaceae are obligate intracellular bacterial pathogens which, depending on the species, cause a wide range of disease in both humans and animals. Members of the this group are the leading cause of bacterial sexually transmitted disease in humans, the leading cause of infectious preventable blindness in developing countries and a major source of community acquired pneumonia, bronchitis and sinusitis. Related Chlamydia pathogens are responsible for similar diseases in ruminants, cats, birds and rodents. In women, untreated Chlamydia genital infections can result in devastating consequences such as pelvic inflammatory disease, ectopic pregnancy, and infertility. Chlamydia trachomatis infections are also strongly epidemiologically linked to increased rates in cervical cancer, the second most common cancer of women worldwide.
Chlamydia undergo a tightly regulated developmental cycle which begins with the infection of the host cell by the metabolically inert, spore-like elementary body (EB). Upon infection, the EB differentiates to the non-infectious metabolically active reticulate body (RB) which divides repeatedly by binary fission within a pathogen modified endocytic vacuole. After multiple rounds of binary fission a subset of RBs differentiate back to the EB which in turn infect neighboring cells upon release by cell lysis or inclusion extrusion.
My laboratory pursues two main areas of interest:
- understand the cytological effects of infection on the host cell, and
- understand and dissect the mechanisms of chlamydial differentiation with an eye to developing novel genetic tools in this difficult to manipulate pathogen.
