Navigation Links
Study illuminates how the plague bacteria causes disease

The bacteria responsible for the plague and some forms of food poisoning "paralyze" the immune system of their hosts in an unexpected way, according to a new study in the September 8, 2006 issue of the journal Cell, published by Cell Press.

The researchers found that these bacteria, which belong to the genus Yersinia, harbor a protein that mimics an apparently unrelated mammalian enzyme. That copycat protein blocks host cells' capacity to change shape and move, abilities important for cells of the immune system to track down and "eat" foreign invaders, the researchers explained.

The discovery marks the second way in which this protein, called YpkA, compromises the immune system. Earlier studies suggested that another portion of YpkA--which may have been derived from a mammalian enzyme and later co-opted by Yersinia--has activity that also influences cell shape by a separate, though incompletely understood mechanism.

The findings offer important new insight into the factors that lend Yersinia their ability to spawn disease, the researchers said. The results might also contribute to new strategies for fighting the bug.

"Yersinia injects several virulence factors into its host," said C. Erec Stebbins of Rockefeller University. "If we can discover which ones are critical, we might identify the pathogen's Achilles heel--an attractive target for antibacterial or anti-virulence compounds."

"We were quite excited to see such a critical and unexpected factor in the virulence of Yersinia--a bacteria historically responsible for some of the worst diseases," he added. Although improvements in sanitation have eliminated acute problems from diseases caused by Yersinia, concerns remain about the possibility that an untreatable strain might arise or that the bacteria might come into use as a biological weapon, he said.

Nearly 200 million people are estimated to have died in the plague epidemics that devastated the ancient world, the researchers said. The successful weaponization of plague in the former Soviet Union bioweapons program also made the pathogen a primary biodefense concern. Additional medical concerns have arisen from the evolution of multidrug-resistant strains of the plague bacterium found in patients from several locations.

The plague bacterium Yersinia pestis is closely related to Y. enterocolitica and Y. pseudotuberculosis, which are food-borne agents that cause inflammation of the stomach and intestines. All Yersinia bacteria have a virulence plasmid, which is necessary to cause disease. Plasmids are extra DNA molecules frequently found in bacteria containing genes that can be passed from one bacterial strain to another and that may confer an evolutionary advantage, such as antibiotic resistance.

In the case of Yersinia, the plasmid harbors numerous genes, including a large number that contribute to the ability of diverse pathogens to deliver virulence factors into host cells. One of these genes is YpkA, a protein with multiple domains, including one closely related to an enzyme, a type of kinase, not typically found in bacteria. Earlier studies found that mutations that eliminate this activity reduce but do not eliminate YpkA's ability to disrupt cell shape by modifying their cytoskeletal support system.

In the current study, the researchers solved the high-resolution crystal structure of a second YpkA domain, the "Rho-GTPase binding domain" along with the host protein, "Rac1," with which it interacts.

"The Yersinia structure was doing things to Rac1 that the host proteins normally do," Stebbins said, suggesting that the domain acted as a mimic.

Further examination confirmed the domain to be a mimic of mammalian "guanidine nucleotide dissociation inhibitor" (GDI) proteins with a critical role in the bacteria's ability to disrupt cell structure. The domain paralyzes cells by acting as an "off-switch" for host proteins involved in modify ing cell shape, Stebbins said.

Mutations that prevented the bacterial proteins' interaction with the host protein significantly impaired YpkA's ability to disrupt the cytoskeleton. Moreover, a mutant strain of Y. pseudotuberculosis that lacked the GDI activity caused significantly fewer problems for infected mice compared to normal bacteria.

"Earlier studies that focused only on the protein's kinase activity had missed half the picture," Stebbins said. "The GDI domain seems to have an even bigger effect on host cells in culture, and a significant impact on virulence."

The results also add to broader themes in the evolution of bacterial diseases, the researchers added.

"It is becoming increasingly clear that a common strategy used by bacterial pathogens to manipulate host cell biology is the mimicry of their own biochemical processes," Stebbins said.


'"/>

Source:Cell Press


Related biology news :

1. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
2. Emory Study Tests Bone Marrow Stem Cells to Improve Circulation in Legs
3. UCLA Study Shows One-Third of Drug Ads in Medical Journals Do Not Contain References Supporting Medical Claims
4. Study Demonstrates Gene Expression Microarrays are Comparable and Reproducible
5. Study Links Ebola Outbreaks To Animal Carcasses
6. Breakthrough Microarray-based Technology for the Study of Cancer
7. NYU Study Reveals How Brains Immune System Fights Viral Encephalitis
8. Study finds more than one-third of human genome regulated by RNA
9. Leukemia Drug Breakthrough Study In New England Journal Of Medicine
10. Study identifies predictors of HIV drug resistance in patients beginning triple therapy
11. New Study from Affymetrix Laboratories Points to Changing View of How Genome Works
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/27/2016)... Research and Markets has announced the addition ... to their offering. The report ... to grow at a CAGR of 12.28% during the period 2016-2020. ... in-depth market analysis with inputs from industry experts. The report covers ... The report also includes a discussion of the key vendors operating ...
(Date:6/22/2016)... , June 22, 2016  The American College of Medical ... Show Executive Magazine as one of the fastest-growing trade ... 25-27 at the Bellagio in Las Vegas ... highest percentage of growth in each of the following categories: ... companies and number of attendees. The 2015 ACMG Annual Meeting ...
(Date:6/22/2016)... , June 22, 2016   Acuant ... and verification solutions, has partnered with RightCrowd ... solutions for Visitor Management, Self-Service Kiosks and ... products that add functional enhancements to existing ... corporations and venues with an automated ID ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... -- The Biodesign Challenge (BDC), a university competition that asks ... systems and biotechnology, announced its winning teams at the ... York City . The teams, chosen ... MoMA,s Celeste Bartos Theater during the daylong summit. Keynote ... of architecture and design, and Suzanne Lee , ...
(Date:6/23/2016)... ... June 23, 2016 , ... In a new case report published today ... a patient who developed lymphedema after being treated for breast cancer benefitted from an ... paradigm for dealing with this debilitating, frequent side effect of cancer treatment. ...
(Date:6/23/2016)... , June 23, 2016 On Wednesday, ... at 4,833.32, down 0.22%; the Dow Jones Industrial Average edged ... closed at 2,085.45, down 0.17%. Stock-Callers.com has initiated coverage on ... ), Nektar Therapeutics (NASDAQ: NKTR ), Aralez Pharmaceuticals ... (NASDAQ: BIND ). Learn more about these stocks ...
(Date:6/23/2016)... June 22, 2016  Amgen (NASDAQ: AMGN ... QB3@953 life sciences incubator to accelerate the ... shared laboratory space at QB3@953 was created to help ... obstacle for many early stage organizations - access to ... sponsorship, Amgen launched two "Amgen Golden Ticket" awards, providing ...
Breaking Biology Technology: