{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/110763"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/110763","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Secondary problems caused by the oxyr response to hydrogen peroxide stress in Escherichia coli","abstract":"Escherichia coli resides in the lumen of the gut, where it encounters both biotic and abiotic sources of hydrogen peroxide stress. Hydrogen peroxide (H2O2) diffuses into cells, where it reacts with iron via Fenton chemistry. Three cellular targets are damaged: DNA, mononuclear iron enzymes, and [4Fe-4S] cluster enzymes. E. coli uses the transcription factor OxyR to sense and respond to H2O2 stress. When the intracellular H2O2 levels rise to 0.2 μM, OxyR is activated via the formation of a disulfide bond, and it induces the transcription of the OxyR regulon. The induced genes include those that scavenge H2O2, reduce the intracellular iron level, and repair the H2O2-mediated damage. Dps, a mini ferritin, is induced by OxyR and it sequesters the free-iron pool, thereby reducing Fenton chemistry. However, this sequestration also causes secondary problems because cells require iron to metallate the iron-dependent enzymes in different biosynthetic pathways. Therefore, OxyR induces the chaperones ClpS and ClpA, which are a part of the Clp family of proteases. Together with the ClpX chaperone and the ClpP protease, ClpSA helps increase the intracellular iron levels, enabling the repair of the [4Fe-4S] enzyme isopropylmalate isomerase. Thus, H2O2-stressed cells maintain a delicate balance of the intracellular iron pools, keeping them low enough to minimize DNA damage but high enough to repair the damaged iron-dependent enzymes. It seemed plausible that the prolonged induction of the OxyR regulon would cause other secondary problems. Indeed, the constitutive expression of OxyR—even in the absence of H2O2 stress—results in growth defects, which seem to arise due to defects in several amino acid biosynthetic pathways and the tricarboxylic acid cycle. Interestingly, these defects do not seem to be due to iron starvation, as evidenced by the lower activities not only of the iron-dependent enzyme fumarase A but also of the iron-independent enzyme isocitrate dehydrogenase. These cells are also unable to transition smoothly out of prolonged stationary phase. Single-gene deletions of various members of the OxyR regulon did not identify the gene involved, suggesting that several genes may be contributing to the growth defect, although the mechanism remains unclear. Alternatively, it is possible that the correct gene has not yet been tested.","abstract_html":"Escherichia coli resides in the lumen of the gut, where it encounters both biotic and abiotic sources of hydrogen peroxide stress. Hydrogen peroxide (H2O2) diffuses into cells, where it reacts with iron via Fenton chemistry. Three cellular targets are damaged: DNA, mononuclear iron enzymes, and [4Fe-4S] cluster enzymes. E. coli uses the transcription factor OxyR to sense and respond to H2O2 stress. When the intracellular H2O2 levels rise to 0.2 μM, OxyR is activated via the formation of a disulfide bond, and it induces the transcription of the OxyR regulon. The induced genes include those that scavenge H2O2, reduce the intracellular iron level, and repair the H2O2-mediated damage. Dps, a mini ferritin, is induced by OxyR and it sequesters the free-iron pool, thereby reducing Fenton chemistry. However, this sequestration also causes secondary problems because cells require iron to metallate the iron-dependent enzymes in different biosynthetic pathways. Therefore, OxyR induces the chaperones ClpS and ClpA, which are a part of the Clp family of proteases. Together with the ClpX chaperone and the ClpP protease, ClpSA helps increase the intracellular iron levels, enabling the repair of the [4Fe-4S] enzyme isopropylmalate isomerase. Thus, H2O2-stressed cells maintain a delicate balance of the intracellular iron pools, keeping them low enough to minimize DNA damage but high enough to repair the damaged iron-dependent enzymes. It seemed plausible that the prolonged induction of the OxyR regulon would cause other secondary problems. Indeed, the constitutive expression of OxyR—even in the absence of H2O2 stress—results in growth defects, which seem to arise due to defects in several amino acid biosynthetic pathways and the tricarboxylic acid cycle. Interestingly, these defects do not seem to be due to iron starvation, as evidenced by the lower activities not only of the iron-dependent enzyme fumarase A but also of the iron-independent enzyme isocitrate dehydrogenase. These cells are also unable to transition smoothly out of prolonged stationary phase. Single-gene deletions of various members of the OxyR regulon did not identify the gene involved, suggesting that several genes may be contributing to the growth defect, although the mechanism remains unclear. Alternatively, it is possible that the correct gene has not yet been tested.","abstract_has_math":false,"creators":["Sen, Ananya"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Microbiology","degree_department":null,"school":null,"contributors":["Imlay, James","Kehl-Fie, Thomas","Metcalf, William","Vanderpool, Carin"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-09-17T04:03:53Z","date_published":"2021-09-17T04:03:53Z","updated_at":"2026-07-22T22:24:52Z","subjects":["ClpSA, ClpX, Dps, OxyR"],"languages":["en"],"rights":["Copyright 2021 Ananya Sen"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/110763","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Imlay, James","Kehl-Fie, Thomas","Metcalf, William","Vanderpool, Carin"]},{"key":"dc:creator","label":"Author","values":["Sen, Ananya"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2021-09-17T04:03:53Z","2023-09-17T04:07:01Z","2021-01-19","2021-05"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["ClpSA, ClpX, Dps, OxyR"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2021 Ananya Sen"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/110763"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Escherichia coli resides in the lumen of the gut, where it encounters both biotic and abiotic sources of hydrogen peroxide stress. Hydrogen peroxide (H2O2) diffuses into cells, where it reacts with iron via Fenton chemistry. Three cellular targets are damaged: DNA, mononuclear iron enzymes, and [4Fe-4S] cluster enzymes. E. coli uses the transcription factor OxyR to sense and respond to H2O2 stress. When the intracellular H2O2 levels rise to 0.2 μM, OxyR is activated via the formation of a disulfide bond, and it induces the transcription of the OxyR regulon. The induced genes include those that scavenge H2O2, reduce the intracellular iron level, and repair the H2O2-mediated damage. Dps, a mini ferritin, is induced by OxyR and it sequesters the free-iron pool, thereby reducing Fenton chemistry. However, this sequestration also causes secondary problems because cells require iron to metallate the iron-dependent enzymes in different biosynthetic pathways. Therefore, OxyR induces the chaperones ClpS and ClpA, which are a part of the Clp family of proteases. Together with the ClpX chaperone and the ClpP protease, ClpSA helps increase the intracellular iron levels, enabling the repair of the [4Fe-4S] enzyme isopropylmalate isomerase. Thus, H2O2-stressed cells maintain a delicate balance of the intracellular iron pools, keeping them low enough to minimize DNA damage but high enough to repair the damaged iron-dependent enzymes. It seemed plausible that the prolonged induction of the OxyR regulon would cause other secondary problems. Indeed, the constitutive expression of OxyR—even in the absence of H2O2 stress—results in growth defects, which seem to arise due to defects in several amino acid biosynthetic pathways and the tricarboxylic acid cycle. Interestingly, these defects do not seem to be due to iron starvation, as evidenced by the lower activities not only of the iron-dependent enzyme fumarase A but also of the iron-independent enzyme isocitrate dehydrogenase. These cells are also unable to transition smoothly out of prolonged stationary phase. Single-gene deletions of various members of the OxyR regulon did not identify the gene involved, suggesting that several genes may be contributing to the growth defect, although the mechanism remains unclear. Alternatively, it is possible that the correct gene has not yet been tested.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2023-05-01","The student, Ananya Sen, accepted the attached license on 2021-01-15 at 10:19.","The student, Ananya Sen, submitted this Dissertation for approval on 2021-01-15 at 10:25.","This Dissertation was approved for publication on 2021-01-19 at 17:03.","DSpace SAF Submission Ingestion Package generated from Vireo submission #16149 on 2021-09-16 at 20:06:30","Made available in DSpace on 2021-09-17T04:03:53Z (GMT). No. of bitstreams: 2 SEN-DISSERTATION-2021.pdf: 6146502 bytes, checksum: e8bb07a5219868684225114d050f6010 (MD5) LICENSE.txt: 4207 bytes, checksum: 2ab87058e219a9cdd058a8bf107de4ac (MD5) Previous issue date: 2021-01-19","Embargo set by: Seth Robbins for item 118608 Lift date: 2023-09-17T04:04:53Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 118608 Lift date: 2023-09-17T04:07:01Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Secondary problems caused by the oxyr response to hydrogen peroxide stress in Escherichia coli"]}]}],"canonical_facts":{"dc:contributor":["Imlay, James","Kehl-Fie, Thomas","Metcalf, William","Vanderpool, Carin"],"dc:creator":["Sen, Ananya"],"dc:date":["2021-09-17T04:03:53Z","2023-09-17T04:07:01Z","2021-01-19","2021-05"],"dc:description":["Escherichia coli resides in the lumen of the gut, where it encounters both biotic and abiotic sources of hydrogen peroxide stress. Hydrogen peroxide (H2O2) diffuses into cells, where it reacts with iron via Fenton chemistry. Three cellular targets are damaged: DNA, mononuclear iron enzymes, and [4Fe-4S] cluster enzymes. E. coli uses the transcription factor OxyR to sense and respond to H2O2 stress. When the intracellular H2O2 levels rise to 0.2 μM, OxyR is activated via the formation of a disulfide bond, and it induces the transcription of the OxyR regulon. The induced genes include those that scavenge H2O2, reduce the intracellular iron level, and repair the H2O2-mediated damage. Dps, a mini ferritin, is induced by OxyR and it sequesters the free-iron pool, thereby reducing Fenton chemistry. However, this sequestration also causes secondary problems because cells require iron to metallate the iron-dependent enzymes in different biosynthetic pathways. Therefore, OxyR induces the chaperones ClpS and ClpA, which are a part of the Clp family of proteases. Together with the ClpX chaperone and the ClpP protease, ClpSA helps increase the intracellular iron levels, enabling the repair of the [4Fe-4S] enzyme isopropylmalate isomerase. Thus, H2O2-stressed cells maintain a delicate balance of the intracellular iron pools, keeping them low enough to minimize DNA damage but high enough to repair the damaged iron-dependent enzymes. It seemed plausible that the prolonged induction of the OxyR regulon would cause other secondary problems. Indeed, the constitutive expression of OxyR—even in the absence of H2O2 stress—results in growth defects, which seem to arise due to defects in several amino acid biosynthetic pathways and the tricarboxylic acid cycle. Interestingly, these defects do not seem to be due to iron starvation, as evidenced by the lower activities not only of the iron-dependent enzyme fumarase A but also of the iron-independent enzyme isocitrate dehydrogenase. These cells are also unable to transition smoothly out of prolonged stationary phase. Single-gene deletions of various members of the OxyR regulon did not identify the gene involved, suggesting that several genes may be contributing to the growth defect, although the mechanism remains unclear. Alternatively, it is possible that the correct gene has not yet been tested.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2023-05-01","The student, Ananya Sen, accepted the attached license on 2021-01-15 at 10:19.","The student, Ananya Sen, submitted this Dissertation for approval on 2021-01-15 at 10:25.","This Dissertation was approved for publication on 2021-01-19 at 17:03.","DSpace SAF Submission Ingestion Package generated from Vireo submission #16149 on 2021-09-16 at 20:06:30","Made available in DSpace on 2021-09-17T04:03:53Z (GMT). No. of bitstreams: 2 SEN-DISSERTATION-2021.pdf: 6146502 bytes, checksum: e8bb07a5219868684225114d050f6010 (MD5) LICENSE.txt: 4207 bytes, checksum: 2ab87058e219a9cdd058a8bf107de4ac (MD5) Previous issue date: 2021-01-19","Embargo set by: Seth Robbins for item 118608 Lift date: 2023-09-17T04:04:53Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 118608 Lift date: 2023-09-17T04:07:01Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Author requested closed access (OA after 2yrs) in Vireo ETD system","Limited"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/110763"],"dc:language":["en"],"dc:rights":["Copyright 2021 Ananya Sen"],"dc:subject":["ClpSA, ClpX, Dps, OxyR"],"dc:title":["Secondary problems caused by the oxyr response to hydrogen peroxide stress in Escherichia coli"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Microbiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:52Z"}