{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:24:54Z","timestamp":1785252294168,"version":"3.55.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Superoxide is a toxic byproduct of aerobic cellular respiration. The cellular regulation of bacterial responses to superoxide stress remains incompletely understood. The present work established an\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    cell model for superoxide stress by deleting superoxide dismutase (SOD) SodA and SodB. Proteomic analysis revealed that SOD deficiency not only induced high expression of the oxidative stress regulator SoxSR but also upregulated the catalase KatE and the organic peroxidases Tpx and BtuE, suggesting that SOD deficiency leads to the subsequent production of multiple reactive oxygen species. Further analysis of central carbon metabolism networks showed that SOD deficiency suppressed oxidative phosphorylation, thereby reducing superoxide production. SOD defects stimulated the pentose phosphate pathway (PPP) and its downstream pathways involved in histidine and phenylalanine synthesis, as well as fatty acid degradation pathway. SOD deficiency rendered\n                    <jats:italic>E. coli<\/jats:italic>\n                    more sensitive to the lethal effects of exogenous hydrogen peroxide. CRISPR-mediated deletion of\n                    <jats:italic>zwf<\/jats:italic>\n                    to block PPP, deletion of\n                    <jats:italic>hisD<\/jats:italic>\n                    and\n                    <jats:italic>pheA<\/jats:italic>\n                    to disrupt histidine and phenylalanine synthesis, or deletion of\n                    <jats:italic>fadE<\/jats:italic>\n                    to block fatty acid degradation, all increased the SOD mutant\u2019s sensitivity to hydrogen peroxide. The absence of\n                    <jats:italic>fadE<\/jats:italic>\n                    , rather than\n                    <jats:italic>hisD<\/jats:italic>\n                    or\n                    <jats:italic>pheA<\/jats:italic>\n                    , further reduced the survival of\n                    <jats:italic>zwf<\/jats:italic>\n                    -SOD mutant under H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    killing. These data indicate that the PPP and fatty acid degradation pathways help SOD-deficient cells respond to oxidative stress. Overall, our findings offer new perspectives on bacterial defenses against oxidative stress and survival strategies.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1793871","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T10:12:49Z","timestamp":1773137569000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Despite inducing antioxidant regulation, superoxide dismutase deficiency makes Escherichia coli more sensitive to hydrogen peroxide"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuejuan","family":"Nong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, Department of Laboratory Medicine, School of Public Health, Xiamen University","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Qiao","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, School of Life Sciences, Inner Mongolia University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, Department of Laboratory Medicine, School of Public Health, Xiamen University","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, The Affiliated Hospital of Yunnan University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, Department of Laboratory Medicine, School of Public Health, Xiamen University","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e15979","DOI":"10.1371\/journal.pone.0015979","article-title":"The Escherichia coli BtuE protein functions as a resistance determinant against reactive oxygen species.","volume":"6","author":"Arenas","year":"2011","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.bbrc.2010.07.002","article-title":"The Escherichia coli btuE gene, encodes a glutathione peroxidase that is induced under oxidative stress conditions.","volume":"398","author":"Arenas","year":"2010","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"B3","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/bs.vh.2022.09.002","article-title":"The antioxidant glutathione.","volume":"121","author":"Averill-Bates","year":"2023","journal-title":"Vitam. Horm"},{"key":"B4","doi-asserted-by":"publisher","first-page":"360438","DOI":"10.1155\/2014\/360438","article-title":"Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxid. Med. Cell Longev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"4202","DOI":"10.1074\/jbc.274.7.4202","article-title":"Why superoxide imposes an aromatic amino acid auxotrophy on Escherichia coli. The transketolase connection.","volume":"274","author":"Benov","year":"1999","journal-title":"J. Biol. Chem"},{"key":"B6","doi-asserted-by":"publisher","first-page":"21037","DOI":"10.1074\/jbc.271.35.21037","article-title":"The mechanism of the auxotrophy for sulfur-containing amino acids imposed upon Escherichia coli by superoxide.","volume":"271","author":"Benov","year":"1996","journal-title":"J. Biol. Chem"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3019","DOI":"10.1021\/ja00451a028","article-title":"A study of the superoxide radical chemistry by stopped-flow radiolysis and radiation induced oxygen consumption.","volume":"99","author":"Bielski","year":"1977","journal-title":"JACS"},{"key":"B8","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1073\/pnas.77.1.347","article-title":"Organ chemiluminescence: noninvasive assay for oxidative radical reactions.","volume":"77","author":"Boveris","year":"1980","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"B9","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1128\/jb.131.3.815-820.1977","article-title":"Intracellular localization of the superoxide dismutases of Escherichia coli: a reevaluation.","volume":"131","author":"Britton","year":"1977","journal-title":"J. Bacteriol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1006\/abbi.1995.1262","article-title":"Dihydroxy-acid dehydratase, a [4Fe-4S] cluster-containing enzyme in Escherichia coli: effects of intracellular superoxide dismutase on its inactivation by oxidant stress.","volume":"319","author":"Brown","year":"1995","journal-title":"Arch. Biochem. Biophys"},{"key":"B11","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1002\/j.1460-2075.1986.tb04256.x","article-title":"Isolation of superoxide dismutase mutants in Escherichia coli: is superoxide dismutase necessary for aerobic life?","volume":"5","author":"Carlioz","year":"1986","journal-title":"EMBO J"},{"key":"B12","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3390\/antiox6040082","article-title":"On the origin of superoxide dismutase: an evolutionary perspective of superoxide-mediated redox signaling.","volume":"6","author":"Case","year":"2017","journal-title":"Antioxidants"},{"key":"B13","doi-asserted-by":"publisher","first-page":"17215","DOI":"10.1016\/S0021-9258(17)44891-5","article-title":"Characterization of Escherichia coli cells deficient in 1-acyl-sn-glycerol-3- phosphate acyltransferase activity.","volume":"265","author":"Coleman","year":"1990","journal-title":"J. Biol. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/s0070-2137(01)80005-4","article-title":"Superoxide dismutase, oxidative stress, and cell metabolism.","volume":"36","author":"Culotta","year":"2000","journal-title":"Curr. Top. Cell Regul"},{"key":"B15","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/0968-0004(82)90151-7","article-title":"Is superoxide important in oxygen poisoning?","volume":"7","author":"Fee","year":"1982","journal-title":"Trends Biochem. Sci."},{"key":"B16","first-page":"43","volume-title":"Cibe Foundation Series 65.","author":"Fitzsimons","year":"1979"},{"key":"B17","doi-asserted-by":"crossref","first-page":"25547","DOI":"10.1016\/S0021-9258(19)74426-3","article-title":"The inactivation of dihydroxy-acid dehydratase in Escherichia coli treated with hyperbaric oxygen occurs because of the destruction of its Fe-S cluster, but the enzyme remains in the cell in a form that can be reactivated.","volume":"268","author":"Flint","year":"1993","journal-title":"J. Biol. Chem."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mam.2008.08.006","article-title":"Glutathione: overview of its protective roles, measurement, and biosynthesis.","volume":"30","author":"Forman","year":"2009","journal-title":"Mol. Aspects Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1146\/annurev.bi.64.070195.000525","article-title":"Superoxide radical and superoxide dismutases.","volume":"64","author":"Fridovich","year":"1995","journal-title":"Annu. Rev. Biochem"},{"key":"B20","doi-asserted-by":"publisher","first-page":"501","DOI":"10.3390\/antiox11030501","article-title":"Superoxide radicals in the execution of cell death.","volume":"11","author":"Fujii","year":"2022","journal-title":"Antioxidants"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1016\/S0021-9258(18)52319-X","article-title":"Superoxide sensitivity of the Escherichia coli 6-phosphogluconate dehydratase.","volume":"266","author":"Gardner","year":"","journal-title":"J. Biol. Chem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"19328","DOI":"10.1016\/S0021-9258(18)55001-8","article-title":"Superoxide sensitivity of the Escherichia coli aconitase.","volume":"266","author":"Gardner","year":"","journal-title":"J Biol Chem"},{"key":"B23","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1046\/j.1365-2958.1999.01343.x","article-title":"The regulation and role of the periplasmic copper, zinc superoxide dismutase of Escherichia coli.","volume":"32","author":"Gort","year":"1999","journal-title":"Mol. Microbiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1128\/JB.180.6.1402-1410.1998","article-title":"Balance between endogenous superoxide stress and antioxidant defenses.","volume":"180","author":"Gort","year":"1998","journal-title":"J. Bacteriol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"6181","DOI":"10.1073\/pnas.87.16.6181","article-title":"Positive control of a global antioxidant defense regulon activated by superoxide-generating agents in Escherichia coli.","volume":"87","author":"Greenberg","year":"1990","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1111\/j.1365-2958.2010.07520.x","article-title":"The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide.","volume":"79","author":"Gu","year":"2011","journal-title":"Mol. Microbiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1111\/mmi.12263","article-title":"Superoxide poisons mononuclear iron enzymes by causing mismetallation.","volume":"89","author":"Gu","year":"2013","journal-title":"Mol. Microbiol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"24253","DOI":"10.1016\/S0021-9258(18)35758-2","article-title":"Functional differences between manganese and iron superoxide dismutases in Escherichia coli K-12.","volume":"267","author":"Hopkin","year":"1992","journal-title":"J. Biol. Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1146\/annurev.micro.57.030502.090938","article-title":"Pathways of oxidative damage.","volume":"57","author":"Imlay","year":"2003","journal-title":"Annu. Rev. Microbiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1146\/annurev.biochem.77.061606.161055","article-title":"Cellular defenses against superoxide and hydrogen peroxide.","volume":"77","author":"Imlay","year":"2008","journal-title":"Annu. Rev. Biochem"},{"key":"B31","doi-asserted-by":"publisher","first-page":"6957","DOI":"10.1016\/S0021-9258(20)89596-9","article-title":"Assay of metabolic superoxide production in Escherichia coli.","volume":"266","author":"Imlay","year":"1991","journal-title":"J. Biol. Chem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1128\/jb.174.3.953-961.1992","article-title":"Suppression of oxidative envelope damage by pseudoreversion of a superoxide dismutase-deficient mutant of Escherichia coli.","volume":"174","author":"Imlay","year":"1992","journal-title":"J. Bacteriol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/j.bbalip.2018.06.017","article-title":"Cardiolipin synthases of Escherichia coli have phospholipid class specific phospholipase D activity dependent on endogenous and foreign phospholipids.","volume":"1863","author":"Jeucken","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.1128\/AEM.04023-14","article-title":"Multigene editing in the Escherichia coli genome via the CRISPR-Cas9 system.","volume":"81","author":"Jiang","year":"2015","journal-title":"Appl. Environ. Microbiol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"6782","DOI":"10.1128\/jb.177.23.6782-6790.1995","article-title":"Superoxide and the production of oxidative DNA damage.","volume":"177","author":"Keyer","year":"1995","journal-title":"J. Bacteriol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"13635","DOI":"10.1073\/pnas.93.24.13635","article-title":"Superoxide accelerates DNA damage by elevating free-iron levels.","volume":"93","author":"Keyer","year":"1996","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"B37","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1046\/j.1365-2958.2002.02719.x","article-title":"A potential role for periplasmic superoxide dismutase in blocking the penetration of external superoxide into the cytosol of Gram-negative bacteria.","volume":"43","author":"Korshunov","year":"2002","journal-title":"Mol. Microbiol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/0891-5849(94)90239-9","article-title":"The role of O2.- in the production of HO.: in vitro and in vivo.","volume":"16","author":"Liochev","year":"1994","journal-title":"Free Radic. Biol. Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"6049","DOI":"10.1016\/S0021-9258(18)63504-5","article-title":"Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein).","volume":"244","author":"McCord","year":"1969","journal-title":"J. Biol. Chem."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1073\/pnas.68.5.1024","article-title":"An enzyme-based theory of obligate anaerobiosis: the physiological function of superoxide dismutase.","volume":"68","author":"McCord","year":"1971","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"B41","doi-asserted-by":"publisher","first-page":"3913","DOI":"10.1128\/JB.187.12.3913-3920.2005","article-title":"Deletion of the datA site does not affect once-per-cell-cycle timing but induces rifampin-resistant replication.","volume":"187","author":"Morigen, Molina","year":"2005","journal-title":"J. Bacteriol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1089\/152308603768295140","article-title":"Functions of thiol-disulfide oxidoreductases in E. coli: redox myths, realities, and practicalities.","volume":"5","author":"Ortenberg","year":"2003","journal-title":"Antioxid. Redox Signal"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.3390\/biom12081019","article-title":"Degradation of exogenous fatty acids in Escherichia coli.","volume":"12","author":"Pavoncello","year":"2022","journal-title":"Biomolecules"},{"key":"B44","doi-asserted-by":"publisher","first-page":"148992","DOI":"10.1016\/j.gene.2024.148992","article-title":"Uncovering the effects of non-lethal oxidative stress on replication initiation in Escherichia coli.","volume":"933","author":"Qiao","year":"","journal-title":"Gene"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2968","DOI":"10.3390\/ijms26072968","article-title":"Characterizing common factors affecting replication initiation during H2O2 exposure and genetic mutation-induced oxidative stress in Escherichia coli.","volume":"26","author":"Qiao","year":"","journal-title":"Int. J. Mol. Sci"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1126\/science.150.3703.1548","article-title":"Glyoxylate in fatty-acid metabolism.","volume":"150","author":"Rabin","year":"1965","journal-title":"Science"},{"key":"B47","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1146\/annurev.micro.55.1.21","article-title":"Roles of thiol-redox pathways in bacteria.","volume":"55","author":"Ritz","year":"2001","journal-title":"Annu. Rev. Microbiol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"e25573","DOI":"10.1371\/journal.pone.0025573","article-title":"Glucose-6-phosphate dehydrogenase protects Escherichia coli from tellurite-mediated oxidative stress.","volume":"6","author":"Sandoval","year":"2011","journal-title":"PLoS One"},{"key":"B49","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1021\/ar00072a005","article-title":"How super is superoxide?","volume":"14","author":"Sawyer","year":"1981","journal-title":"Account. Chem. Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"4286","DOI":"10.1128\/jb.170.9.4286-4292.1988","article-title":"Transcriptional regulation of katE in Escherichia coli K-12.","volume":"170","author":"Schellhorn","year":"1988","journal-title":"J. Bacteriol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"7173","DOI":"10.1128\/JB.183.24.7173-7181.2001","article-title":"Alkyl hydroperoxide reductase is the primary scavenger of endogenous hydrogen peroxide in Escherichia coli.","volume":"183","author":"Seaver","year":"","journal-title":"J. Bacteriol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"7182","DOI":"10.1128\/JB.183.24.7182-7189.2001","article-title":"Hydrogen peroxide fluxes and compartmentalization inside growing Escherichia coli.","volume":"183","author":"Seaver","year":"","journal-title":"J. Bacteriol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e0309988","DOI":"10.1371\/journal.pone.0309988","article-title":"Evidence for endogenous hydrogen peroxide production by E. coli fatty acyl-CoA dehydrogenase.","volume":"19","author":"Sirithanakorn","year":"2024","journal-title":"PLoS One"},{"key":"B54","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/s0167-4781(97)00044-4","article-title":"Identification and analysis of the rpoS-dependent promoter of katE, encoding catalase HPII in Escherichia coli.","volume":"1352","author":"Tanaka","year":"1997","journal-title":"Biochim. Biophys. Acta"},{"key":"B55","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1126\/science.aad4017","article-title":"Complementation of mitochondrial electron transport chain by manipulation of the NAD+\/NADH ratio.","volume":"352","author":"Titov","year":"2016","journal-title":"Science"},{"key":"B56","doi-asserted-by":"publisher","first-page":"4197","DOI":"10.1128\/jb.172.8.4197-4205.1990","article-title":"soxR, a locus governing a superoxide response regulon in Escherichia coli K-12.","volume":"172","author":"Tsaneva","year":"1990","journal-title":"J. Bacteriol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.cmet.2020.02.017","article-title":"Serine catabolism feeds NADH when respiration is impaired.","volume":"31","author":"Yang","year":"2020","journal-title":"Cell Metab."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1793871\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T10:12:50Z","timestamp":1773137570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1793871\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":57,"alternative-id":["10.3389\/fmicb.2026.1793871"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1793871","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"article-number":"1793871"}}