Fifty years ago, infectious diseases were declining in the developed world in response to antibiotics and vaccines. By the late 20th century however, the incidence of infectious diseases had increased dramatically in many parts of the world and the pace continues to accelerate.
Dr. Paumet’s laboratory studies the pathogenesis of Chlamydia trachomatis, which is the most frequently reported bacterial sexually transmitted disease in the US, and the leading cause of infectious blindness worldwide. An estimated 92 million new cases of infection per year occur worldwide, with ~2 million in the USA alone. Noticeably, the numbers of new infections as well as the associated healthcare costs, which now exceed $4 billion annually in the US, have been rising since the late 1980s. This emphasizes the urgency in identifying new therapeutic bacterial targets. However, to accomplish this, a fundamental understanding of Chlamydia’s survival strategies is crucial. Dr. Paumet’s laboratory seeks to understand the mechanisms that Chlamydia uses to establish its infectious compartment inside host cells.
Chlamydia is particularly difficult to cure, partly due to its intracellular lifestyle. While non-intracellular bacteria can be naturally destroyed by the immune system, intracellular bacteria hide inside human cells to escape immune defenses. To achieve this, Chlamydia manipulates host cells to create an intracellular niche in which it can multiply. In particular, Chlamydia is a master at manipulating host intracellular vesicular trafficking, and is one of the most skilled pathogens at co-opting eukaryotic membrane fusion. In eukaryotic cells, membrane fusion is driven by specific proteins called SNAREs. Dr. Paumet’s team discovered that Chlamydia mimics elements of this fusion machinery through the expression of SNARE-like proteins, and was the first to publish that these Chlamydial SNARE-like proteins are capable of interfering with the host SNARE fusion machinery to block membrane fusion.
Dr. Paumet’s research on Chlamydia pathogenesis has been federally funded through the National Institutes of Health (NIH) since its inception. After having unraveled the basic mechanism used by Chlamydia to block certain vesicular pathways, the Paumet laboratory is now using a multidisciplinary approach to understand mechanisms at the molecular/atomic level. Combining crystallographic analysis with a variety of sophisticated functional assays will facilitate determination of how chlamydial proteins are able to interfere with their host partners. Ultimately these results will open new avenues of research for other intracellular bacteria including Salmonella and Mycobacterium that also manipulate the host vesicular trafficking to their advantage.