Bacterial pathogens

The best cell biologists on earth are not people — they are microbes!

Neisseria gonorrhoeae and Neisseria meningitidis

Neisseria gonorrhoeae attaching to the apical surface of a human epithelial cell. Transmission electron micrograph: P. Stenberg and A. Merz.

After a long hiatus we have re-started our work on these closely-related Gram negative bacteria, that cause gonorrhea and meningitis. As a grad student Alex worked on the type 4 pilus and on how host cells respond when Neisseria adhere, using these filamentous appendages.

In the experiment shown below, laser tweezers are used to hold a small bead near bacteria which are anchored to a larger bead. The bacterial pili (not visible by transmitted light microscopy) reach out and repeatedly pull the bead out of the optical trap, toward the bacteria.

Type 4 pili are among the most remarkable machines in nature. Acting as grappling hooks, they can feed out a filament, attach to a surface, and reel the filament in, like a grappling hook. In collaboration with Mike Sheetz, we were the first to directly demonstrate pilus retraction, in experiments using laser tweezers (optical gradient trapping). Not long after that, Jeff Skerker and Howard Berg used total internal reflection microscopy to watch the type 4 pili of Pseudomonas extending and retracting. Now we are working to understand the biochemical mechanisms used by these pathogens to assemble and retract pili, and how they attach to host cells. In our current experiments we’re focusing on biochemical approaches.

Here’s an amazing animation depicting how the type 4 pilus might extend and retract, from Grant Jensen’s lab at Caltech:

• Bacterial secreted effectors

Over the last decade we’ve collaborated with the Mougous group here at UW on studies of bacterial type VI effectors used to kill other bacteria, and to manipulate host cells. In addition, we are using bacterial effectors as tools in our studies of transport through the Golgi.

• Virology

We have thoughts. Perhaps in the near future, results. Time will tell!