Discovery of a new mechanism used by pathogenic bacteria to disable host defenses

February 18, 2015, Ludwig Maximilian University of Munich
Credit: AG Jung

Ludwig Maximilian University of Munich researchers report the discovery of a new mechanism used by pathogenic bacteria to disable host defenses: Addition of a sugar residue at a specific position within the translation factor EF-P boosts the production of toxic proteins.

The translation factor EF-P plays an important role in the regulation of . Depending on the precise amino-acid sequence specified by the RNA blueprints that direct protein synthesis, the cell's "protein factories" – known as ribosomes – sometimes stall before a given protein is complete. EF-P is required to restart the production line by relieving this kind of premature halt. Studies carried out on a variety of have previously shown that the restart process is crucial for the completion of proteins that are deleterious to the infected host. Thus, strains that lack EF-P turn out to be significantly less virulent than those in which the protein is functionally competent. Furthermore, EF-P can trigger the resumption of protein synthesis at a stalling site only if it has been chemically modified at a certain position by specific bacterial enzymes. "We have now discovered a previously unknown modification mechanism that is utilized by bacteria to activate EF-P," says LMU microbiologist Kirsten Jung.

Addition of an activating sugar residue

Jung's team has shown that, in a number of clinically significant pathogens, EF-P is activated by the addition of a sugar unit (monosaccharide) called rhamnose to the amino acid arginine located at a specific position in this protein. In chemical terms, this arginine is "rhamnosylated". "To the best of our knowledge, this is the first time that anyone has detected this particular form of in bacteria," says Jürgen Lassak, first author on the new study. EF-P is not restricted to bacteria. Related versions of the protein are also found in the Archaea, as well as in eukaryotes. In a previous collaboration with the group led by Daniel Wilson at LMU's Gene Center, Jung and her colleagues had elucidated the mechanism of activation of EF-P in the enterobacterium Escherichia coli, which is a part of microbiota in humans. Their latest cooperative project, carried out under the auspices of the Excellence Cluster CIPSM with which both Jung and Wilson are affiliated, builds upon and supplements the earlier work. "In E. coli, EF-P is modified in quite a different way, and the enzymes necessary to catalyze the reaction are found in only 25% of all bacterial species. So the new study significantly extends the range of bacteria in which the mode of activation of EF-P is now known," Jung explains.

Possible target for antibiotics

In light of the ever increasing incidence of multiply resistant strains among pathogenic bacterial species, new classes of antibiotics are urgently needed, and the new findings suggest that the rhamnosylation reaction might offer a point of attack for novel antibacterial drugs. "Arginine rhamnosylation occurs in clinically relevant bacterial pathogens, such as Pseudomonas aeruginosa and Neisseria, which often display resistance to several different classes of antibiotic," Lassak points out. "If we can find a way to specifically inhibit this mechanism, this would certainly provide a considerable stimulus to the search for new therapeutic agents." The researchers plan to follow up this lead, and will also investigate whether proteins other than EF-P are subject to arginine rhamnosylation. Looking farther into the future, Jung speculates that "it might even be possible to exploit this modification in the context of synthetic biology, to modify the biochemical properties and physiological functions of proteins in useful ways."

Explore further: Raising the blockade

More information: "Arginine-rhamnosylation as new strategy to activate translation elongation factor P" Nature Chemical Biology (2015) DOI: 10.1038/nchembio.1751

Related Stories

Raising the blockade

December 14, 2012

At crucial points in the metabolism of all organisms, a protein with the unwieldy name of Translation Elongation Factor P (EF-P, for short) takes center stage. What it actually does during protein synthesis has only now been ...

Piloting ribosomes past proline pairs

September 10, 2013

Certain proteins are known to require Translation Factor EF-P for their synthesis, and a new study enlarges the size of the set. As some of its members are involved in bacterial pathogenicity, the results are also of therapeutic ...

Infection biology: The elusive third factor

June 22, 2012

Researchers from Ludwig-Maximilians-Universität (LMU) in Munich have identified an enzyme that is involved in a modification pathway that is essential for bacterial pathogenicity. Because it shows no similarity to other ...

Achilles' heel of pathogenic bacteria discovered

December 17, 2012

Multidrug-resistant bacteria remain a major concern for hospitals and nursing homes worldwide. Propagation of bacterial resistance is alarming and makes the search for new antimicrobials increasingly urgent. Scientists at ...

Recommended for you

Two new planets discovered using artificial intelligence

March 26, 2019

Astronomers at The University of Texas at Austin, in partnership with Google, have used artificial intelligence (AI) to uncover two more hidden planets in the Kepler space telescope archive. The technique shows promise for ...

Infertility's roots in DNA packaging

March 26, 2019

Pathological infertility is a condition affecting roughly 7 percent of human males, and among those afflicted, 10 to 15 percent are thought to have a genetic cause. However, pinpointing the precise genes responsible for the ...

Facebook is free, but should it count toward GDP anyway?

March 26, 2019

For several decades, gross domestic product (GDP), a sum of the value of purchased goods, has been a ubiquitous yardstick of economic activity. More recently, some observers have suggested that GDP falls short because it ...

Droughts could hit aging power plants hard

March 26, 2019

Older power plants with once-through cooling systems generate about a third of all U.S. electricity, but their future generating capacity will be undercut by droughts and rising water temperatures linked to climate change. ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.