Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Salmonella stays deadly with a 'beta' version of cell behavior

15.08.2011
Salmonella cells have hijacked the protein-building process to maintain their ability to cause illness, new research suggests.

Scientists say that these bacteria have modified what has long been considered typical cell behavior by using a beta form of an amino acid – as opposed to an alpha form – during the act of making proteins.

Beta versions of amino acids occur in nature under rare and specific circumstances, but have never been observed as part of protein synthesis. Before this finding, in fact, researchers had determined that virtually all proteins were constructed with the alpha forms of amino acids.

This work has shown that when researchers delete any one of three genes from the process that makes use of the beta form of the amino acid, or if they insert the alpha form in the beta version's place, Salmonella cells are no longer able to cause disease. The amino acid in question is lysine, one of 22 genetically encoded amino acids that are strung together in cells to make proteins.

"When these genes were knocked out, the cells became sensitive to antibiotics. And if we put beta lysine into the medium where cells were growing, they became resistant to antibiotics," said Michael Ibba, professor of microbiology at Ohio State University and a senior author of the study. "So we could see the beta amino acid being taken up and used. The cells really do need the beta amino acid to be resistant to antibiotics, and for other aspects of their virulence."

This finding suggests that the process using this specific beta amino acid could be an attractive antibiotic target for this common pathogen, the researchers say.

The Centers for Disease Control and Prevention estimates that about 1.4 million people in the United States are infected with Salmonella each year, though only 40,000 cases are reported. Most people infected with Salmonella develop diarrhea, fever and abdominal cramps. Though recovery can occur within a week without treatment, some severe cases require antibiotic treatment and hospitalization.

The study is published in the Aug. 14 online edition of the journal Nature Chemical Biology.

This work began when University of Toronto scientists exploring the origins of Salmonella's virulence identified three genes that were clear players in the process. These three genes – called YjeK, PoxA and EF-P – were unusual in this context.

Genes that confer virulence in bacteria typically have a specific job, such as producing toxins or transporters. But these three virulence genes all looked like they should have a role in the protein synthesis machinery – which is Ibba's expertise.

Under normal circumstances in cells, an enzyme will select amino acids in the cell and place them on a molecule called transfer RNA, or tRNA, which leads to translation of the genetic code into proteins.

In Salmonella cells, these steps are similar, but with a few surprising twists, Ibba said. He and colleagues confirmed that the YjeK gene makes beta lysine, and showed that the PoxA gene takes that beta lysine and attaches it to EF-P – a protein that partially mimics the shape and function of tRNA.

"It's a really unexpected pathway," said Ibba, also an investigator in Ohio State's Center for RNA Biology. "It is a mimic of what normally makes protein in a cell. Where a cell would normally be expected to use an alpha amino acid, Salmonella puts on a beta amino acid. And it ends up making molecules that lead to the cells being virulent."

The research team first reconstructed this unusual protein synthesis process in test tube experiments, and then followed with studies in cell cultures. Even before they took on studying the mechanism, however, they knew that the effects of these virulence genes were powerful: In earlier animal studies, deleting any one of the three genes and then infecting mice with these altered Salmonella cellshad no effect on the animals. When the genes were left intact and cells were injected into mice, the resulting Salmonella infection killed the animals.

In addition, when the researchers tricked Salmonella cells into using alpha lysine for this pathway instead of beta lysine, the cells lost their ability to cause illness.

"This tells us the cell is not going to be able to easily replace the beta amino acid," Ibba said. "It is essential for virulence in Salmonella."

And that, he said, is why that amino acid might be such an effective drug target, especially as humans don't seem to make beta amino acids at all. "You have to make an antibiotic look like something natural, only different. If you have something that's already different like a beta amino acid, you've potentially got a much better drug target because it involves chemistry that's comparatively rare in the cell. It's harder for the cell to try to alter its own chemistry to develop resistance," Ibba said.

From here, the researchers are observing cell behavior later in the protein-building process to figure out how this hijacked system actually gives Salmonella its virulence.

This work is supported by the National Institutes of Health, the Canada Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and Ohio State.

Co-authors include Hervé Roy, a former Ohio State research scientist now at the University of Central Florida; S. Betty Zou and William Navarre of the University of Toronto; Tammy Bullwinkle of Ohio State's Department of Microbiology; and Benjamin Wolfe and Craig Forsyth of Ohio State's Department of Chemistry.

Contact: Michael Ibba, (614) 292-2120; Ibba.1@osu.edu
Written by Emily Caldwell, (614) 292-8310; Caldwell.151@osu.edu

Michael Ibba | EurekAlert!
Further information:
http://www.osu.edu

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Researchers invent tiny, light-powered wires to modulate brain's electrical signals

21.02.2018 | Life Sciences

The “Holy Grail” of peptide chemistry: Making peptide active agents available orally

21.02.2018 | Life Sciences

Atomic structure of ultrasound material not what anyone expected

21.02.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>