An Acid-tolerance Response System Protecting Exponentially Growing Escherichia coli

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    E.coli has developed variable acidic stress response systems. Acid resistance (AR) systemsresponse to extreme acid stress has been investigated in previous study. However, the mechanism towards mild and moderate acid stress is not clear enough. In this research, we propose a new acid-tolerance response (ATR) system that can help E. coli adapt to and grow at pH 4.0-5.0. In theory this mechanism could promote the colonization of pathogenic E. coli in the gut. Therefore, it has major implications for clinical practice and research.


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    Food poisoning is generally caused by the intake of a food or drink contaminated with food-borne pathogenic bacteria, such as Salmonella, Escherichia coli, Listeria, and Campylobacter (1). These bacteria, without exception, must first colonize the intestinal before causing disease. With pH values as low as 1.5-2.5, the stomach has been recognized as a natural antibiotic barrier. With their passage into the small intestine, cells will encounter a less acidic environment (pH 4.0-6.0) with the presence of organic acids produced by the normal intestinal flora(2). The acidic stress response systems has been extensively studied in Escherichia coli. So we know E. coli is able to survive in stomach owing to its ability to induce an acid resistance (AR) systems under this extreme acidic condition. Up to now, five AR systems, AR1-AR5, are reported. However, understanding how E. coli can grow and colonize the intestinal remains a fundamental question. Because the molecular mechanism of acidic stress response under a mild acid stress is not fully understood.

    In this paper, we propose a new acid-tolerance Response (ATR) system, and unravel how exponentially growing E. coli adapt to a mild acid condition (pH4.0-5.0) . The two-component system CpxRA is involved in the process by directly sensing acidification  through protonation of the CpxA periplasmic histidine residues, and thus activates transcription of the essential genes fabA and fabB in biosynthesis of unsaturated fatty acids (UFAs) to enhance the UFAs content in membrane lipid (Fig.1).


Fig. 1. An overview of acid-tolerance Response (ATR) system



    Mouse experiments confirmed that this ATR system significantly promotes E. coli survival in mouse intestinal lumens. Another interesting fact is that this ATR system functioning in exponential phase is highly conserved across bacteria species, such as Salmonella, Klebsiella and so on. These findings indicate that ATR system may be a potential therapeutic target and be able to serve as a possible direction for the development of antibacterial drugs.

   In bio-production of organic acid, ATR system could enhance E. coli tolerance to acid environments. So in-depth investigation of ATR system would be beneficial not only for keeping the growth under acid condition , but also enhancing the production of organic acid. It exhibits a great potential for large-scale industrial production.


  1. Hedberg Craig. Food-Related Illness and Death in the United States[J]. Emerging Infectious Diseases, 5(6):840-841.
  2. Lin J, Smith MP, Chapin KC, Baik HS, Bennett GN, Foster JW. Mechanisms of acid resistance in enterohemorrhagic Escherichia coli. Appl Environ Microbiol 62, 686 3094-3100 (1996).
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zhao zhe

doctoral studies, University of Chinese Academy of Sciences

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