{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:13:30Z","timestamp":1785420810965,"version":"3.56.0"},"reference-count":81,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2026,4,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Uropathogenic\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      (UPEC) is the leading causative agent of urinary tract infection (UTI). Copper (Cu) is a host effector mobilized to the bladder during the innate immune response activated by acute UTI.\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      precisely regulates Cu homeostasis via efflux systems because excess Cu is toxic. Long-chain fatty acid (LCFA) homeostasis is critical for the survival of\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      during envelope stress. However, the interaction between LCFA metabolism and survival during Cu stress, which is also known to induce envelope stress, is not known and is the subject of this report. We hypothesized that fatty acid homeostasis is critical for the survival of UPEC during Cu toxicity and modulates UPEC virulence during UTI. A reverse genetic screen of the KEIO collection identified FabR and FadR as critical proteins for optimal survival of\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      during Cu stress. FadR and FabR regulate transcription genes involved in LCFA metabolism. By using targeted deletion mutants and genetic complementation, we demonstrate that LCFA metabolism affects survival of UPEC during Cu stress. Cell-associated Cu concentrations were decreased in the\n                      <jats:italic toggle=\"yes\">\u0394fadR<\/jats:italic>\n                      mutant, and we found that the expression of Cu detoxification genes was upregulated in these mutants. UPEC lacking FadR were more sensitive to superoxide stress compared to the wild-type strain. Liquid chromatography-mass spectrometry (LC-MS) analysis revealed that lipid saturation levels were increased in UPEC during Cu stress in a\n                      <jats:italic toggle=\"yes\">fabR-<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">fadR<\/jats:italic>\n                      -dependent manner. Furthermore, both mutants displayed lower flagellar expression and attenuated fitness during UTI in the mouse model. Together, our findings demonstrate that LCFA homeostasis is a crucial mediator of Cu homeostasis and UPEC virulence during UTI.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Uropathogenic\n                        <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                        (UPEC) is the primary causative agent of urinary tract infection (UTI). Previous research has established that UPEC experiences copper stress during UTI, and resistance to copper is critical for UPEC virulence. Envelope stress response systems are activated by copper (Cu) stress, and long-chain fatty acid (LCFA) homeostasis is critical for the survival of\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        during envelope stress. However, the interaction between LCFA metabolism and Cu stress is not known. Our results demonstrate that LCFA homeostasis is a crucial mediator of copper homeostasis in UPEC and modulates UPEC virulence during UTI.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00117-26","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:09:42Z","timestamp":1774876182000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Long-chain fatty acid homeostasis contributes to survival of uropathogenic\n                    <i>E. coli<\/i>\n                    during copper toxicity"],"prefix":"10.1128","volume":"208","author":[{"given":"Michael","family":"Teve","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01f5ytq51","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Veterinary Pathobiology, School of Veterinary Medicine and Biomedical Sciences, Texas A&M 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