The Koch Lab @ Texas A&M
- Department of Biology -
How single bacteria grab and squeeze the host during infections?
Welcome to the Koch Lab! We ask fundamental biological questions about how bacterial cells infect host tissue. Our multidisciplinary approaches leverage the arsenal of genetic and molecular tools, advanced super-resolution and force probing microscopy techniques, as well as biophysical modeling and computer simulations.
At the center of our research is our recent discovery that the clinically important human pathogen Pseudomonas aeruginosa uses molecular scale fingers to squeeze and probe its mechanical environment much like we humans do when we squeeze a fruit with our fingers. This process allows P. aeruginosa to feel the rigidity of the environment similar to our sense of touch and to tune its virulence to substrate stiffness. We investigate this novel link between mechanical properties of the infection sites and the pathogenicity of bacteria across the whole scale: from the actual molecular mechanism to the physiological consequences for the pathogen and the infected tissue cell.
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TFP are remarkable biological machines. About ten components form a static complex. The carefully concerted interaction of three molecular motors and several dynamically interacting regulators gives rise to the dynamic cycles of pilus extension and retraction (see video) that drive many important biological functions like DNA uptake and virulence. We try to reverse engineer and film how this machine is constructed by the cell and how its dynamics are regulated using advanced microscopy techniques.
The sense of touch is crucial for humans and allows us for example to check if a fruit is ripe. We gently squeeze the fruit (think an avocado or peach) with our fingers and know that only a soft fruit is ready to eat.
We recently discovered that bacteria have a similar ability using TFP as molecular scale fingers to deform and probe its growth substrate. We try to understand how this process is regulated molecularly and by the environment. We use clever techniques to visualize nano-meter small substrate deformations (see video) and measure the fores of individual TFP for targeted mutants that we generate in our lab.
Remarkably, stiffness sensing in P. aeruginosa tunes the key transcription factor Vfr, which controls over 100 virulence related genes. This suggests that P. aeruginosa is able to distinguish its broad spectrum of infection sites by substrate mechanics to modulate virulence specifically to each site. This novel connection between pathogenicity and mechanical properties of the infection site thus presents tremendous potential for both clinical applications and new biophysical insights into mechanosensing.
We are currently developing new experimental approaches to investigate this potential fruitful avenue of fundamental clinical research.