Abstract

The extremely acidic environment of the mammalian stomach, with a pH range usually between 1 and 3, represents a stressful challenge for enteric pathogenic bacteria such as Escherichia coli before they enter into the intestine. The hdeA gene of E. coli was found to be acid inducible and was revealed by genetic studies to be important for the acid survival of the strain. This study was performed in an attempt to characterize the mechanism of the activity of the HdeA protein. Our data provided in this report strongly suggest that HdeA employs a novel strategy to modulate its chaperone activity: it possesses an ordered conformation that is unable to bind denatured substrate proteins under normal physiological conditions (i.e. at neutral pH) and transforms into a globally disordered conformation that is able to bind substrate proteins under stress conditions (i.e. at a pH below 3). Furthermore, our data indicate that HdeA exposes hydrophobic surfaces that appear to be involved in the binding of denatured substrate proteins at extremely low pH values. In light of our observations, models are proposed to explain the action of HdeA in both a physiological and a molecular context.

Highlights

  • The extremely acidic environment of the mammalian stomach, with a pH range usually between 1 and 3, represents a stressful challenge for enteric pathogenic bacteria such as Escherichia coli before they enter into the intestine

  • This study represents a major effort to understand how HdeA, a periplasmic protein found to be required for E. coli cells to survive in acidic environments, works to prevent the aggregation of proteins at extremely low pH values

  • Experimental observations include the following: (a) HdeA exhibits chaperone-like activity, i.e. being able to bind to the denatured substrate proteins, exclusively at extremely low pH values and releases them at neutral pH; (b) HdeA possesses a globally disordered conformation at extremely low pH values but an ordered conformation at neutral pH; and (c) HdeA exposes hydrophobic surfaces that appear to be involved in binding denatured substrate proteins at extremely low pH values

Read more

Summary

Introduction

The extremely acidic environment of the mammalian stomach, with a pH range usually between 1 and 3, represents a stressful challenge for enteric pathogenic bacteria such as Escherichia coli before they enter into the intestine.

Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call