{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T07:55:13Z","timestamp":1786866913001,"version":"build-2736575974"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2026,1,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The arginine-dependent acid resistance (Adi) system is a vital component that enables\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      and other enterobacteria to withstand the extreme acidity in the human gastrointestinal tract. It consists of the proton-consuming decarboxylation of arginine, catalyzed by AdiA, and the uptake of arginine, as well as the excretion of the more alkaline agmatine, catalyzed by the antiporter AdiC. The corresponding genes\n                      <jats:italic toggle=\"yes\">adiA<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">adiC<\/jats:italic>\n                      are induced in\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      under acidic conditions (pH &lt; 5.5), a process that is tightly regulated by the AraC\/XylS transcriptional activator AdiY. Here, we show that the pH-sensing mechanism of AdiY functions through the protonation of two histidines (His34 and His60) in the N-terminal domain. Replacing these histidine residues with alanine, glutamine, or aspartate abolishes the pH-dependent activation of AdiY, both\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      , as demonstrated by promoter-reporter assays, and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , as indicated by the loss of DNA-binding activity detected by surface plasmon resonance spectroscopy. Biochemical analyses of purified wild-type AdiY using size-exclusion chromatography and intrinsic tryptophan fluorescence revealed a pronounced and reversible pH-dependent conformational change that does not occur in the pH-sensing\u2013deficient AdiY variant. A model is proposed in which AdiY forms a monomer at physiological pH. At a lower intracellular pH, the protonation of histidine in AdiY causes a conformational change that leads to the binding of AdiY as a tetramer to the DNA. This work elucidates the molecular mechanism of a one-component signal transduction system that combines both sensory and responsive functions.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Throughout their life,\n                        <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                        and other bacteria may encounter acidic environments, for example, when passing through the human stomach. Their chances of survival under these conditions depend on the number and efficiency of acid resistance systems. Although many acid resistance mechanisms have been extensively studied, the molecular mechanism by which bacteria sense low pH is not yet fully understood. This study demonstrates that the transcription factor AdiY acts as a direct pH sensor by using two histidines to detect intracellular acidification in\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        . When these histidines become protonated, AdiY changes its conformation and activates genes that support cell survival under acid stress. These findings not only reveal a new way in which bacteria can perceive extremely low pH environments but also provide the basis for the development of AdiY as a pH reporter.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00542-25","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T14:00:27Z","timestamp":1766498427000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["AdiY acts as a cytoplasmic pH sensor via histidine protonation to regulate acid stress adaptation in\n                    <i>Escherichia 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