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Inducible acid tolerance mechanisms in enteric bacteria
1Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile 36688, USA.
Novartis Foundation Symposium
|April 20, 1999
Summary
Salmonella typhimurium adapts to acid stress using an acid tolerance response (ATR) involving over 50 acid shock proteins (ASPs). Key regulators like Fur, PhoP, and sigma S control this vital survival mechanism.
Area of Science:
- Microbiology
- Bacterial Physiology
- Stress Response Mechanisms
Background:
- Enteric microorganisms possess inducible mechanisms to survive extreme acid stress.
- Salmonella typhimurium exhibits an acid tolerance response (ATR) triggered by mild acid exposure.
- This adaptation involves the induction of over 50 acid shock proteins (ASPs).
Purpose of the Study:
- To elucidate the regulatory network controlling the acid tolerance response (ATR) in Salmonella typhimurium.
- To identify key proteins and pathways involved in bacterial acid resistance.
- To compare acid resistance strategies between Salmonella typhimurium, E. coli, and Shigella.
Main Methods:
- Investigated the role of major regulatory proteins including Fur, PhoP, and sigma S in ATR.
- Analyzed the induction of acid shock proteins (ASPs) under acid stress conditions.
- Examined the function of the Ada protein (O6-methylguanine methyltransferase) in DNA repair after pH stress.
- Compared acid resistance systems in S. typhimurium with those in E. coli and Shigella.
Main Results:
- Eight ASPs are regulated by the iron regulatory protein Fur in an iron-independent manner.
- The two-component regulator PhoP autoinduces and controls three additional ASPs.
- Sigma S, a stress sigma factor, regulates eight ASPs and its induction is linked to reduced ClpXP protease activity.
- Mutations in Fur, PhoP, or sigma S regulators result in a defective ATR.
- The Ada protein is crucial for repairing pH stress-induced DNA damage, as ada mutants show sensitivity to both acid and alkaline conditions.
- E. coli and Shigella utilize different acid resistance systems, including glucose-repressed and decarboxylase-based systems.
Conclusions:
- The ATR in S. typhimurium is a complex, multi-component system regulated by Fur, PhoP, and sigma S.
- These regulators orchestrate the induction of numerous ASPs essential for acid survival.
- DNA repair mechanisms, involving the Ada protein, are critical for mitigating pH stress damage.
- Distinct acid resistance strategies exist among related enteric bacteria like S. typhimurium, E. coli, and Shigella.