Biomechanics of the Swimming and Chemotaxis of the Leptospiraceae

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This award will support research that will improve our understanding of physical aspects of bacteria. Specifically, this work will focus on the bacterium Leptospira interrogans, which is highly invasive. Relatives of this bacterium cause diseases such as Lyme disease and syphilis. This work will explore how specific proteins in the bacterium influence its physical structure and movement, how the bacterium interacts with mammalian-like tissues, and how the bacterium controls its ability to navigate through its hosts. The results of this work will reveal why this bacterium is so efficient at invading mammals and creating infections in them. This work is interdisciplinary, and will use techniques from physics, microbiology, cellular biology, bioengineering, and mathematics. Insights gained from this work will provide new information about the disease processes of this bacterium and related species and may eventually lead to novel therapeutics. The interdisciplinary approach will help broaden participation of underrepresented groups and will be used as an outreach opportunity for lower socio-economic K-12 students at schools in the Tucson area.Spirochete bacteria are long and thin and can propel themselves through fluids and tissues with surprising ease. This motility is driven by internal helical flagella that rotate in between the cell wall and the outer membrane. While past research elucidated some basic mechanisms of spirochete motility, many questions remain elusive. This research examines the bacterium that causes leptospirosis as it has a single flagellum at either end of the cell, thereby allowing direct analysis of the direction of rotation of the flagella and how it is impacted by different alterations and perturbations, while also providing a comparative analysis for previous work that has been done on the Lyme disease spirochete. Specifically, this research will assess the specific role of biophysical parameters and proteins on motility, determine the effect of external environment on movement, and determine whether mechanical cues are involved in chemotaxis. The research will use live cell imaging, optical trapping and other micromanipulation techniques, and computational modeling to explore the general hypothesis that biophysical interactions between the flagella and cell body are a crucial aspect of this bacterium’s ability to invade and infect mammalian hosts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.