Volume 89 Issue 37 | p. 10 | News of The Week
Issue Date: September 12, 2011

Bacterial Acid Trips

Chemical Biology: New technique reveals how pathogens endure our acidic stomachs
Department: Science & Technology
Keywords: bacteria, pathogens, acid

When you get food poisoning, the bacteria causing havoc in your intestines have navigated a rather treacherous journey through your acidic stomach. The molecular mechanisms by which a pathogen survives this acid environment have long kept researchers guessing. But now a team of biochemists led by Peng R. Chen of Peking University, in China, has developed a new technique to study the bacterial coping mechanism (Nat. Chem. Biol., DOI: 10.1038/NChemBio.644).

In addition to helping researchers better understand pathogen survival, the new technique, which permits protein-protein interactions to be studied at low pH, will likely find application in probing the biology that occurs in acidic conditions. To date, studying protein-protein interactions at low pH has been a challenge because most techniques don’t work in strongly acidic environments, Chen explains.

To study how Escherichia coli survives in the stomach, Chen’s group focused on the bacterium’s chaperone proteins, which prevent cellular proteins from unfolding in harmful environments. They engineered the gene for an essential chaperone protein called HdeA so that it incorporates an artificial amino acid (called DiZPK) at the site that binds client proteins. The artificial amino acid has a side chain that possesses an alkyl diazirine moiety that can cross-link to other proteins when irradiated.

The team exposed this engineered E. coli to acid so HdeA would start protecting proteins from denaturation. Then they hit the bacterium with light to trap HdeA with its client proteins and used mass spectrometry to identify these clients.

Among the dozens of client proteins protected by HdeA, the team detected two other chaperone proteins. This finding suggests to them that HdeA is a mother chaperone protein in a large acid-resistance network.

It’s “a very clever and elegant method,” says John W. Foster, a microbiologist who studies pathogen acid resistance at the University of South Alabama. “The real value of this work is in the methodology, which could be used to probe many other chaperone-client interactions in bacteria, archaea, and eukaryotes.”

Indeed, Chen says he’s currently using the approach to examine protein-protein interactions in the lysosome, the organelle in eukaryotes whose acidic interior is responsible for breaking down waste proteins and other cellular molecules.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

Leave A Comment

*Required to comment