Plant and animal bacteria share cell-killing mechanism

November 22, 2000

Black death or black rot: U-M scientists find plant and animal bacteria share same deadly cell-killing mechanism

ANN ARBOR---When it comes to killing cells, Yersinia pestis---the bacterium that causes bubonic plague---is the stealth assassin of the pathogen world. It kills quietly and efficiently by first slipping inside immune system sentinel cells and cutting off the communication lines they need to call for help.

Now scientists at the University of Michigan have discovered the molecular mechanism Yersinia uses to sever these vital cell signaling pathways. It turns out to be an ancient agent of death---so effective that both plant and animal bacteria have been using it throughout long periods of evolutionary history.

Results from the U-M study---completed in collaboration with scientists at the University of California-Berkeley, the State University of New York at Stony Brook and Brookhaven National Laboratory---are published in the Nov. 24 issue of Science.

"YopJ, the protein Yersinia uses to cut cell signaling pathways, is one of six proteins the bacterium injects into immune cells called macrophages," says Jack E. Dixon, Ph.D., the Minor J. Coon Professor of Biological Chemistry in the U-M Medical School and co-director of the U-M's Life Sciences Institute. Every Yop has a specific function and they work together to get inside cells and destroy the body's defense systems.

In research published last year in Science, Dixon's team reported that YopJ attacks two vital cellular signaling pathways called MAPK and NF(B, which regulate immune response and help prevent cell death.

"Now we have found closely related variants of YopJ in several species of pathogenic plant and animal bacteria, as well as in Rhizobium---symbiotic bacteria that live on plant roots," says Dixon, who directed the research project.

When Mary Beth Mudgett, Ph.D., a postdoctoral fellow at the University of California-Berkeley infected leaves with the plant equivalent of YopJ---a protein called AvrBsT---black patches of dead cells appeared around the infection site. "The leaf induces cell death in areas exposed to the bacteria to prevent it from spreading through the entire plant," explains Kim Orth, Ph.D., a research investigator in the U-M Medical School and first author on the Science paper.

Zhaohui Xu, Ph.D., U-M assistant professor of biological chemistry, found that all these plant and animal YopJ-related proteins look like cysteine proteases---specialized enzymes that cut up proteins. Detailed comparisons of the molecular structure of YopJ-related proteins in the study found that they all shared a key catalytic site---four amino acids nestled in a pocket, which must be present for YopJ to do its protein-cutting work. YopJ mutants that lacked even one of these amino acids could not block MAPK pathways and had no effect on macrophage immune response.

Although future research is needed to confirm their hypothesis, Dixon and Orth believe that YopJs disrupt a vital, but previously unappreciated, step in cell signaling pathways called ubiquitination.

"Until recently, scientists believed that ubiquitin proteins simply mark other proteins for destruction," Orth says. "This study shows that ubiquitin-like proteins are required to activate these critical cellular signaling pathways. When YopJ breaks the bond between ubiquitin and its target molecule, the pathway is blocked and cell communication shuts down.

"We still don't know YopJ's target molecule, but at least now we know it must be a member of the ubiquitin protein family," Orth says. Identification of the molecule could have important implications in medicine, Orth adds, because these pathways are critical in development of cancer and immune-related diseases.

The study was funded by the National Institutes of Health, the U.S. Department of Energy and the Walther Cancer Institute. Additional collaborators on the study included Zhao Qin Bao, U-M research associate; Brian Staskawicz, Ph.D., professor of plant and microbial biology at the University of California-Berkeley; Lance E. Palmer, Ph.D., and James B. Bliska, Ph.D., from the State University of New York at Stony Brook, and Walter F. Mangel, Ph.D., a biologist at Brookhaven National Laboratory.
-end-
EDITORS: To reach University of California-Berkeley researchers, contact Catherine Zandonella at (510) 643-7741 or by e-mail to CLZ@pa.urel.berkeley.edu. To reach scientists at Brookhaven National Laboratory, contact Karen McNulty Walsh at (631) 344-8350 or by e-mail to kmcnulty@bnl.gov.

The University of Michigan
News Service
412 Maynard
Ann Arbor, MI 48109-1399
Web: http://www.umich.edu/~newsinfo

University of Michigan

Related Bacteria Articles from Brightsurf:

Siblings can also differ from one another in bacteria
A research team from the University of Tübingen and the German Center for Infection Research (DZIF) is investigating how pathogens influence the immune response of their host with genetic variation.

How bacteria fertilize soya
Soya and clover have their very own fertiliser factories in their roots, where bacteria manufacture ammonium, which is crucial for plant growth.

Bacteria might help other bacteria to tolerate antibiotics better
A new paper by the Dynamical Systems Biology lab at UPF shows that the response by bacteria to antibiotics may depend on other species of bacteria they live with, in such a way that some bacteria may make others more tolerant to antibiotics.

Two-faced bacteria
The gut microbiome, which is a collection of numerous beneficial bacteria species, is key to our overall well-being and good health.

Microcensus in bacteria
Bacillus subtilis can determine proportions of different groups within a mixed population.

Right beneath the skin we all have the same bacteria
In the dermis skin layer, the same bacteria are found across age and gender.

Bacteria must be 'stressed out' to divide
Bacterial cell division is controlled by both enzymatic activity and mechanical forces, which work together to control its timing and location, a new study from EPFL finds.

How bees live with bacteria
More than 90 percent of all bee species are not organized in colonies, but fight their way through life alone.

The bacteria building your baby
Australian researchers have laid to rest a longstanding controversy: is the womb sterile?

Hopping bacteria
Scientists have long known that key models of bacterial movement in real-world conditions are flawed.

Read More: Bacteria News and Bacteria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.