HdeB functions as an acid-protective chaperone in bacteria

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Enteric bacteria like Escherichia coli possess acid response systems to survive the stomach's acidic environment.
• Periplasmic chaperones HdeA and HdeB protect bacterial proteomes from acid-induced damage.
• HdeA is activated at low pH (2), dissociating into monomers, while HdeB shows limited activity at pH 2 and 3.

Purpose of the Study:

• To investigate the physiological role, activation mechanism, and structural requirements of HdeB as a molecular chaperone.
• To compare the distinct acid-response functions of homologous chaperones HdeA and HdeB.

Main Methods:

• Structural and biochemical studies were employed.
• Nuclear Magnetic Resonance (NMR), analytical ultracentrifugation, and fluorescence spectroscopy were utilized.
• Bacterial survival and growth assays under different pH conditions were performed.

Main Results:

• HdeB functions as an effective molecular chaperone, with optimal activity at pH 4.
• Unlike HdeA, HdeB remains largely folded and dimeric at its optimal pH.
• HdeB's dynamic nature at pH 4 facilitates client protein binding, prevents aggregation, and aids refolding.
• Overexpression of HdeA enhances survival at pH 2-3, while HdeB overexpression boosts growth at pH 4.

Conclusions:

• HdeA and HdeB have evolved distinct pH optima and mechanisms for molecular chaperone activity.
• These homologous proteins provide bacteria with a robust defense against a spectrum of acidic conditions.
• The study elucidates the specialized roles of HdeA and HdeB in bacterial acid tolerance.