Mike Manson

Research Interests

Bacteria have a limited behavioral repertoire. Their most conspicuous behavior is chemotaxis – the pursuit of molecules that are favorable to acquire and the avoidance of chemicals that are best to avoid. The simplicity of bacterial motility and chemotaxis and the amenability of the model species Escherichia coli to genetic, biochemical and physiological manipulation have facilitated rapid advances in understanding the molecular mechanisms of biological energy conversion and signal transduction.

Our laboratory studies the inputs and outputs of chemotaxis. Ligands interact with the periplasmic receptor domain of a chemotactic signal transducer that spans the cell membrane. This interaction is converted into an intracellular signal that is communicated to the flagella. Molecules can be sensed either by binding directly to a receptor or by first interacting with a periplasmic binding protein, which then interacts with a receptor.

Our interest has recently focused on two molecules that serve not as nutrients but rather as specific biological signals. One of these is the ubiquitous host neurotransmitter and hormone norepinephrine (NE), about half of which is present in the gastrointestinal tract. We have discovered that E. coli first converts NE into the compound dihydroxymandelic acid (DHMA) by virtue of two enzymes whose production is induced by NE. DHMA then binds to the same site on the serine chemoreceptor Tsr as serine itself to elicit an attractant signal. Concentrations of DHMA as low as 5 nanomolar can be detected. We hypothesize that chemotaxis to NE/DHMA directs motile bacteria, including pathogens, to preferred sites of colonization on the epithelium of the GI tract, suggesting that blocking such chemotaxis may serve as a protective measure against GI tract infection.

The second compound is the quorum-sensing signal, autoinducer-2 (AI-2), which is produced by a wide range of bacteria, including Gram-positive and Gram-negative species. Biofilms are a particularly rich source of AI-2. AI-2 is first recognized by the periplasmic binding protein LsrB, which, after it binds AI-2, interacts with Tsr at a different site than DHMA. Thus, DHMA and AI-2 can be sensed simultaneously. We are studying the possibility that planktonic bacteria are attracted to biofilms by following gradients of AI-2. Intervention in this process may allow inhibition of biofilm formation where it is not desired and production of biofilms where they are desired.