Plastic Protein Protects Bacteria From Stomach Acid's Unfolding Power

Stomach acid aids in food digestion and helps kill disease-causing bacteria. One way that acid kills bacteria is by causing the proteins in them to unfold and stick together in much the same way that heating an egg causes its proteins to form a solid mass. Just as it is virtually impossible for a cook to unboil an egg, it is also very difficult for bacteria to dissolve these protein clumps, so bacteria and most living things can die when exposed to acid or heat.

However, disease-causing bacteria such as the notorious E. coli are protected from stomach acid by a tiny protein called HdeA. In the PNAS paper, James Bardwell and coworkers describe how this protein works to protect bacteria. Like other proteins, HdeA unfolds and becomes more flexible when exposed to acid. But in a clever twist, the unfolding process that inactivates most other proteins activates HdeA. Once unfolded, this plastic protein molds itself to fit other bacterial proteins that have been made sticky by acid- induced unfolding.

"Just as plastic wrappers prevent candies from sticking together, HdeA prevents the unfolded proteins from sticking together and forming clumps," said Bardwell, a professor of molecular, cellular and developmental biology and of biological chemistry, as well as a Howard Hughes Medical Institute Investigator.

Postdoctoral fellow Tim Tapley, who spearheaded the research, said: "HdeA directly senses acid and changes from its inactive to active form within a fraction of a second." Instead of becoming completely unfolded in response to acid and sticking to itself, HdeA is only partially unfolded. It then uses the flexibility it gains through partial unfolding to rapidly become plastic enough to adapt to and bind various damaged proteins. This helps E. coli evade the otherwise deadly effects of stomach acid.

In addition to Bardwell and Tapley, the paper's authors are undergraduate students Jan Körner and Julia Hupfeld, graduate student Madhuri Barge, research investigator Joseph Schauerte, professor of biological chemistry Ari Gafni and associate professor of molecular, cellular and developmental biology Ursula Jakob. The research was funded in part by the National Institutes of Health.

These findings were published online in the Proceedings of the National Academy of Sciences the week of March 23.