How stress hormones guide bacteria into their host – ScienceDaily

A newly discovered protein helps bacteria recognize stress hormones in the human body and direct their movement within the host.

In humans and animals, catecholamines such as epinephrine, norepinephrine, and dopamine are common stress hormones. Stress can increase the body’s susceptibility to bacterial infections. In the laboratory, stress hormones stimulate the growth of various pathogens. This had already been observed in Salmonella (Salmonella enterica serotype Typhimurium) and other intestinal bacteria, Escherichia coli and the causative agent of cholera, Vibrio cholerae. In addition, epinephrine and norepinephrine facilitate the infection of body cells by bacteria. And these hormones also influence the biosynthesis of virulence factors, which allow pathogens to adhere to, enter and destroy cells.

“We therefore suspected that certain bacteria use these hormones as signals to recognize the environment of the eukaryotic host,” explains Professor Kirsten Jung, a microbiologist at LMU. “But the molecular basis was not known.” Together with Professor Stephan A. Sieber of the Technical University of Munich (TUM) and other researchers, Jung has now identified the binding site of epinephrine and epinephrine-derived phenylephrine in the bacterium. Vibrio campbellii. As the team reports in PNAS, the target of both molecules is the CheW protein. “The biological significance of the mechanism is that the bacteria recognize, for example, that they are no longer in seawater, but in the intestine of a host,” says Jung.

Studies with the model organism V. campbellii

“We wanted to know how bacteria recognize catecholamines as signaling molecules,” explains the LMU scientist. “Which receptors control this process? His experiments consisted of several individual stages.

For the study, Sieber developed a method of chemically modifying epinephrine and phenylephrine, so researchers could directly isolate complexes of catecholamines and related bacterial proteins. A prerequisite for the experiments was that the new compounds had no biological characteristics that the unmodified molecules did not have. Jung’s group did laboratory experiments to demonstrate that this was so. Epinephrine binds iron, unlike phenylephrine, a derivative of epinephrine. With their choice of compounds, the researchers wanted to rule out effects that occur when bacteria have a higher iron supply.

Jung and Sieber worked with Vibrio campbellii as a model organism. The marine bacterium infects fish, shrimp, squid and many other marine invertebrates. They added Vibrio campbellii to chemically modified catecholamines and lyse the cells. Then they extracted from the lysate all the proteins to which a molecule had bound and characterized them using proteome analysis. This resulted in a particular enrichment of the soluble chemotaxis protein CheW.

Subsequently, Jung’s group isolated the CheW protein directly from bacteria, purified it, and measured its catecholamine binding affinity. In the process, the researchers discovered something surprising: the hormones do not bind to the chemoreceptors themselves, as originally expected, but to the coupling protein CheW, which sits between the receptors and a cascade of signal transduction. This entire stimulus-perception system controls the movement of the bacterium through a chemical gradient.

“Our study brings new information on the communication of bacteria with their host”, summarizes Jung. “We were able to show that the swimming behavior of bacteria is modified by host hormones, which are controlled by CheW.” Motility, and in particular directed motility, is of decisive importance for the colonization of the host, since bacteria deliberately seek to colonize an organism and conquer all niches. In the next step, Jung now wants to find out whether the same mechanism can be detected in other bacteria.

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