{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:45:00Z","timestamp":1790819100500,"version":"4.1.0"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["231396381\/GRK1947"],"award-info":[{"award-number":["231396381\/GRK1947"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["453440095"],"award-info":[{"award-number":["453440095"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018934","name":"Universit\u00e4t Greifswald","doi-asserted-by":"crossref","award":["K\u00e4the-Kluth-Scholarship"],"award-info":[{"award-number":["K\u00e4the-Kluth-Scholarship"]}],"id":[{"id":"10.13039\/501100018934","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Clostridioides difficile<\/jats:italic>\n              infections have become a major challenge in medical facilities. The bacterium is capable of spore formation allowing the survival of antibiotic treatment. Therefore, research on the physiology of\n              <jats:italic>C. difficile<\/jats:italic>\n              is important for the development of alternative treatment strategies. In this study, we investigated eight putative flavodoxins of\n              <jats:italic>C. difficile<\/jats:italic>\n              630. Flavodoxins are small electron transfer proteins of specifically low potential. The unusually high number of flavodoxins in\n              <jats:italic>C. difficile<\/jats:italic>\n              suggests that they are expressed under different conditions. We determined high transcription levels for several flavodoxins during the exponential growth phase, especially for\n              <jats:italic>floX<\/jats:italic>\n              . Since flavodoxins are capable of replacing ferredoxins under iron deficiency conditions in other bacteria, we also examined their expression in\n              <jats:italic>C. difficile<\/jats:italic>\n              under low iron and no iron levels. In particular, the amount of\n              <jats:italic>fldX<\/jats:italic>\n              increased with decreasing iron concentration and thus could possibly replace ferredoxins. Moreover, we demonstrated that\n              <jats:italic>fldX<\/jats:italic>\n              is increasingly expressed under different oxidative stress conditions and thus may play an important role in the oxidative stress response. While increased\n              <jats:italic>fldX<\/jats:italic>\n              expression was detectable at both RNA and protein level,\n              <jats:italic>CD2825<\/jats:italic>\n              showed increased expression only at mRNA level under H\n              <jats:sub>2<\/jats:sub>\n              O\n              <jats:sub>2<\/jats:sub>\n              stress with sufficient iron availability and may indicate hydroxyl radical-dependent transcription. Although the exact function of the individual flavodoxins in\n              <jats:italic>C. difficile<\/jats:italic>\n              needs to be further investigated, the present study shows that flavodoxins could play an important role in several physiological processes and under infection-relevant conditions.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              The gram-positive, anaerobic, and spore-forming bacterium\n              <jats:italic>Clostridioides difficile<\/jats:italic>\n              has become a vast problem in human health care facilities. The antibiotic-associated infection with this intestinal pathogen causes serious and recurrent inflammation of the intestinal epithelium, in many cases with a severe course. To come up with novel targeted therapies against\n              <jats:italic>C. difficile<\/jats:italic>\n              infections, a more detailed knowledge on the pathogen\u2019s physiology is mandatory. Eight putative flavodoxins, an extraordinarily high copy number of this type of small electron transfer proteins, are annotated for\n              <jats:italic>C. difficile<\/jats:italic>\n              . Flavodoxins are known to be essential electron carriers in other bacteria, for instance, during infection-relevant conditions such as iron limitation and oxidative stress. This work is a first and comprehensive overview on characteristics and expression profiles of the putative flavodoxins in the pathogen\n              <jats:italic>C. difficile<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01895-23","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T13:49:08Z","timestamp":1707227348000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Characterizing the flavodoxin landscape in\n            <i>Clostridioides difficile<\/i>"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4603-7525","authenticated-orcid":false,"given":"Daniel","family":"Troitzsch","sequence":"first","affiliation":[{"name":"Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7274-8252","authenticated-orcid":false,"given":"Robert","family":"Knop","sequence":"additional","affiliation":[{"name":"Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Dittmann","sequence":"additional","affiliation":[{"name":"Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Bartel","sequence":"additional","affiliation":[{"name":"Department of Microbial Proteomics, Institute of Microbiology, University of Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Z\u00fchlke","sequence":"additional","affiliation":[{"name":"Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timon Alexander","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Tr\u00e4n","sequence":"additional","affiliation":[{"name":"Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thadd\u00e4us","family":"Echelmeyer","sequence":"additional","affiliation":[{"name":"Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5457-2552","authenticated-orcid":true,"given":"Susanne","family":"Sievers","sequence":"additional","affiliation":[{"name":"Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, University of Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5514-4"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3020807"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(92)90400-e"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291x(65)90445-6"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0926-6593(66)80025-5"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jxb\/eru273"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2008.07.001"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14077"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405791200"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fenrg.2019.00079"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00098-15"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03183"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.7.1788-1793.2000"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0221881"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01698"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00091-21"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2018.05.018"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/fty010"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1052"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1830"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48786-x"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01488-1"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl124"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2103579118"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01939"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty496"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.4161\/rna.8.1.13346"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2012.04.007"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/fty009"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)41019-2"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01559-20"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14011152"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14456"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00941.x"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi001096c"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi001746c"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.05.047"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi049131t"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/41.2.171"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3170103"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00597-09"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.71.12.8442-8450.2005"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000738"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(95)03532-x"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.02111"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051881"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1110"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac240"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-015-0614-2"},{"key":"e_1_3_4_51_2","first-page":"532","article-title":"A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples","volume":"15","author":"Chomczynski P","year":"1993","unstructured":"Chomczynski P. 1993. A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 15:532\u2013534,","journal-title":"Biotechniques"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12733"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku630"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-10-r99"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr101065j"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10098"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2015.12.003"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/mas.21540"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01895-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01895-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T14:05:31Z","timestamp":1709647531000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.01895-23"}},"subtitle":[],"editor":[{"given":"Meera","family":"Unnikrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,5]]},"references-count":58,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,5]]}},"alternative-id":["10.1128\/spectrum.01895-23"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.01895-23","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,5]]},"assertion":[{"value":"2023-05-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01895-23"}}