Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mechanism uncovered behind Salmonella virulence and drug susceptibility

30.07.2010
Although mechanism had not been recognized before, evidence shows similar mechanism of protein modification occurs in all 5 kingdoms of life

Researchers have discovered a novel mechanism in Salmonella that affects its virulence and its susceptibility to antibiotics by changing its production of proteins in a previously unheard of manner. This allows Salmonella to selectively change its levels of certain proteins to respond to inhospitable conditions.

Although the mechanism had not been recognized before, the scientists were intrigued to find evidence of a similar mechanism in all five kingdoms of life – animals, plants, fungi, protista, and monera.

The findings were published today, July 29, in Molecular Cell. The senior author of the study is Dr. Ferric C. Fang, professor of microbiology, laboratory medicine, and medicine at the University of Washington (UW). Fang also directs the Clinical Microbiology Laboratory at Harborview Medical Center in Seattle. The lead author is William Wiley Navarre, who began the study as a postdoctoral fellow in the Fang lab and is now an assistant professor at the University of Toronto.

Salmonella enters the gut when people eat contaminated food, and can sometimes spread to other parts of the body. Illness outbreaks and grocery recalls related to Salmonella are often in the news. Babies, young children, the elderly, and people with cancer or HIV are especially prone to severe illness from Salmonella.

Salmonella is adaptable and can withstand many of the body's attempts to fight it. The bacteria live and multiply in a special compartment inside the cells of an infected person or animal. Salmonella can alter its physiology as it moves from a free-swimming life to its residence in a host cell. Salmonella's metabolism also changes over time to make use of the nutrients available in the host cell, and to survive damage from the build-up of oxidants and nitric oxide in the infected cell.

While screening mutant Salmonella that were resistant to a form of nitric oxide that normally stops the bacteria from dividing, Navarre, Fang and their research collaborators found mutations in two little-known genes. These are the closely linked poxA and yjeK genes. In a number of bacteria, these two genes are associated with a third gene that encodes the Bacterial Elongation Factor P, which is involved in protein production.

The researchers discovered that these three genes operate in a common pathway that is critical for the ability of the Salmonella bacteria to cause disease and resist several classes of antibiotics. Salmonella with mutations in either the poxA gene or the yjeK genes, the study noted, appear to be nearly identical and show similar changes in proteins involved in metabolism. Strains with mutations in both genes resemble the single mutant strains, an observation that suggests the two genes work in the same pathway.

The mutant strains exhibited many abnormalities under stressful conditions.

"The wide spectrum of compounds that dramatically inhibited the growth of these mutant strains suggest that the defect lies in a general stress response," the researchers noted. The mutant bacteria measurably differed from the wild-type Salmonella under 300 different conditions. In addition, their aberrant production of virulence factors reduces their ability to survive in the host.

The researchers' analysis also suggests that the way poxA and yjeK modify the bacterial protein elongation factor is essential in the production of proteins that allow the bacteria to use alternative energy sources when they are deprived of nutrients, as occurs after they enter host cells.

Unexpectedly the researchers found that the Salmonella with mutations in poxA and yjeK continued to respire inappropriately under nutrient-poor conditions in which wild-type Salmonella cease respiration.

Perhaps the mutant strains don't know when to quit. Wild-type Salmonella might enter a state of suspended animation to weather harsh conditions, whereas the mutants fail to respond properly to environmental stress. The fact that the mutants continue to respire when they are in dire straits might lead to the production of toxic oxygen-containing compounds.

"This might explain," the authors suggested, "why the mutants are broadly sensitive to a large number of unrelated compounds and cellular stresses."

The researchers also noticed a resemblance between the astounding manner in which the poxA gene modifies the bacterial elongation factor to regulate stress resistance, and the way a similarly acting factor is regulated in plant and animal cells.

During the manufacture of a protein, transfer RNA, also called tRNA, normally places an amino acid at the end of a growing chain of protein building blocks. A certain type of enzyme normally hands the tRNA the amino acid for it to place. However, in this study, researchers have shown for the first time that the poxA enzyme steps in and directly attaches an amino acid to the Elongation Factor P protein, rather than to the tRNA.

Fang said, "Sometimes it seems as if the most basic discoveries in biology have already been made. It was fun and unexpected to learn something new about a process as fundamental as protein synthesis."

"This is an interesting illustration of molecular evolution," Fang continued. "This essential, but previously unrecognized mechanism, for regulating the production of proteins appears to have been conserved over evolutionary time and continues to take place in cells belonging to all five kingdoms of life."

Future studies in his lab will address the specific reasons behind the defective stress response in poxA- and yjeK-deficient bacteria and the explanation for its different effects on the amounts of individual proteins. The lab will also look further into the roles of the normal poxA and yjeK proteins, the intriguing way in which the bacterial elongation protein is modified, the apparent universality of this protein-modifying mechanism in living cells and its conservation throughout the course of evolution.

This research was supported by grants from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Navarre also received support from the Damon-Runyon Cancer Foundation and the Canadian Institutes of Health Research.

In addition to Navarre and Fang, the scientists on the study are Shicong Zou, Jinglin Lucy Xie, and Runjan Kumar, all from the Department of Molecular Genetics at the University of Toronto; Herve Roy and Michael Ibba from the Department of Microbiology at The Ohio State University; Alexei Savchenko, Alexander Singer, and Elena Edvokimova from the Banting and Best Institute for Medical Research in Toronto; and Lynne R. Prost from the UW Department of Microbiology.

Leila Gray | EurekAlert!
Further information:
http://www.washington.edu

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>