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Extremely acid-tolerant bacteria, such as\n              <jats:italic>Escherichia coli<\/jats:italic>\n              , survive the strong acid stress, e.g., in the stomach of vertebrates. Recently, we were able to show that the induction of motility genes in\n              <jats:italic>E. coli<\/jats:italic>\n              is strictly dependent on the degree of acid stress, i.e., they are induced under mild acid stress but not under severe acid stress. However, it was not known to what extent fine-tuned expression of motility genes is related to fitness and the ability to survive periods of acid shock. In this study, we demonstrate that the expression of FlhDC, the master regulator of flagellation, is inversely correlated with the acid shock survival of\n              <jats:italic>E. coli<\/jats:italic>\n              . We encountered this phenomenon when analyzing mutants from the Keio collection, in which the expression of\n              <jats:italic>flhDC<\/jats:italic>\n              was altered by an insertion sequence element. These results suggest a fitness trade-off between acid tolerance and motility.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                <jats:italic>Escherichia coli<\/jats:italic>\n                is extremely acid-resistant, which is crucial for survival in the gastrointestinal tract of vertebrates. Recently, we systematically studied the response of\n                <jats:italic>E. coli<\/jats:italic>\n                to mild and severe acidic conditions using Ribo-Seq and RNA-Seq. We found that motility genes are induced at pH 5.8 but not at pH 4.4, indicating stress-dependent synthesis of flagellar components. In this study, we demonstrate that motility-activating mutations upstream of\n                <jats:italic>flhDC<\/jats:italic>\n                , encoding the master regulator of flagella genes, reduce the ability of\n                <jats:italic>E. coli<\/jats:italic>\n                to survive periods of acid shock. Furthermore, we show an inverse correlation between motility and acid survival using a chromosomal isopropyl \u03b2-D-thio-galactopyranoside (IPTG)-inducible\n                <jats:italic>flhDC<\/jats:italic>\n                promoter and by sampling differentially motile subpopulations from swim agar plates. These results reveal a previously undiscovered trade-off between motility and acid tolerance and suggest a differentiation of\n                <jats:italic>E. coli<\/jats:italic>\n                into motile and acid-tolerant subpopulations, driven by the integration of insertion sequence elements.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.00544-24","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T13:01:38Z","timestamp":1713877298000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Motility-activating mutations upstream of\n            <i>flhDC<\/i>\n            reduce acid shock survival of\n            <i>Escherichia coli<\/i>"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-301X","authenticated-orcid":false,"given":"Kilian","family":"Schumacher","sequence":"first","affiliation":[{"name":"Faculty of Biology, Microbiology, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7565-6841","authenticated-orcid":false,"given":"Djanna","family":"Braun","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Microbiology, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-0252","authenticated-orcid":false,"given":"Karin","family":"Kleigrewe","sequence":"additional","affiliation":[{"name":"Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS), Technical University of Munich, Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0779-6841","authenticated-orcid":false,"given":"Kirsten","family":"Jung","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Microbiology, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507535103"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jobm.3620370506"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuac037"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.39.2.686-703.1983"},{"key":"e_1_3_4_6_2","first-page":"183","article-title":"Intraluminal pH of the human gastrointestinal tract","volume":"46","author":"Fallingborg J","year":"1999","unstructured":"Fallingborg J. 1999. 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