Bacterial Stress Reliever

THE OVERALL STRUCTURE of the stressosome, probably one of the most complex regulatory machines in bacteria, has been obtained for the first time. The findings could lead to the use of stressosomes as drug delivery systems or bionanotechnology scaffolds, says a director of the study, structural biologist Richard J. Lewis of Newcastle University, in England.

Bacteria survive under all sorts of conditions in part by using the 1.8-megadalton stressosome to sense and react to problems such as adverse pH and salinity changes. The stressosome senses stress signals and reacts to them by activating sigma B, a transcription factor that boosts production of proteins that help reduce the stresses. The complex includes several proteins: one RsbS, five RsbR variants, and one RsbT (regulators of sigma B protein S, R, and T, respectively).

The high-resolution crystal structures of some of these proteins had previously been determined. Now, Lewis, microscopist Marin van Heel of Imperial College London, and coworkers have used cryoelectron microscopy to fit these structures into a lower resolution model of the entire stressosome (Science 2008, 322, 92).

This model suggests a mechanism in which the stressosome's RsbR-RsbS core analyzes incoming signals from 20 stress-sensing RsbR appendages and induces RsbT to activate sigma B. The response may vary with stress severity, the researchers suggest.

The new model "is clever and an interesting starting point for thinking about how the stressosome might be able to integrate potentially diverse stress signals to produce a cumulative output," comments William G. Haldenwang, a sigma B activation expert at the University of Texas Health Science Center at San Antonio.

"We have come a long way from the 'bag of enzymes' biochemical mentality of the past that was used to describe bacteria," says signal transduction specialist James A. Hoch of Scripps Research Institute, adding that targeting stressosomes may represent "the new frontier in the design of antibacterial drugs."