{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:17:40Z","timestamp":1787163460290,"version":"build-2736575974"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | NIH | National Institute of Dental and Craniofacial Research","award":["DE026758"],"award-info":[{"award-number":["DE026758"]}]},{"name":"HHS | NIH | National Institute of Dental and Craniofacial Research","award":["T90DE030860"],"award-info":[{"award-number":["T90DE030860"]}]},{"name":"HHS | NIH | National Institute of Dental and Craniofacial Research","award":["DE030895"],"award-info":[{"award-number":["DE030895"]}]},{"name":"HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","award":["T32AI007323"],"award-info":[{"award-number":["T32AI007323"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,1,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The Gram-negative oral pathobiont\n                    <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                    can traverse to extra-oral sites such as placenta and colon, promoting adverse pregnancy outcomes and colorectal cancer, respectively. How this anaerobe sustains many metabolically changing environments enabling its virulence potential remains unclear. Informed by our genome-wide transposon mutagenesis, we report here that the highly conserved\n                    <jats:italic>\n                      <jats:underline>R<\/jats:underline>\n                      hodobacter\n                    <\/jats:italic>\n                    <jats:underline>n<\/jats:underline>\n                    itrogen-\n                    <jats:underline>f<\/jats:underline>\n                    ixation (Rnf) complex, encoded by the\n                    <jats:italic>rnfCDGEAB<\/jats:italic>\n                    gene cluster, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of the Rnf complex via non-polar, in-frame deletion of\n                    <jats:italic>rnfC<\/jats:italic>\n                    (\u0394\n                    <jats:italic>rnfC<\/jats:italic>\n                    ) abrogates polymicrobial interaction (or coaggregation) associated with adhesin RadD and biofilm formation. The defect in coaggregation is not due to reduced cell surface of RadD, but rather an increased level of extracellular lysine, which binds RadD and inhibits coaggregation. Indeed, removal of extracellular lysine via washing \u0394\n                    <jats:italic>rnfC<\/jats:italic>\n                    cells restores coaggregation, while addition of lysine inhibits this process. These phenotypes mirror that of a mutant (\u0394\n                    <jats:italic>kamA<\/jats:italic>\n                    ) that fails to metabolize extracellular lysine. Strikingly, the \u0394\n                    <jats:italic>rnfC<\/jats:italic>\n                    mutant is defective in ATP production, cell growth, cell morphology, and expression of the enzyme MegL that produces hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) from cysteine. Targeted metabolic profiling demonstrated that catabolism of many amino acids, including histidine and lysine, is altered in \u0394\n                    <jats:italic>rnfC<\/jats:italic>\n                    cells, thereby reducing production of ATP and metabolites including H\n                    <jats:sub>2<\/jats:sub>\n                    S and butyrate. Most importantly, we show that the \u0394\n                    <jats:italic>rnfC<\/jats:italic>\n                    mutant is severely attenuated in a mouse model of preterm birth. The indispensable function of Rnf complex in fusobacterial pathogenesis via modulation of bacterial metabolism makes it an attractive target for developing therapeutic intervention.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      This paper illuminates the significant question of how the oral commensal\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      adapts to the metabolically changing environments of several extra-oral sites such as placenta and colon to promote various diseases as an opportunistic pathogen. We demonstrate here that the highly conserved\n                      <jats:italic>\n                        <jats:underline>R<\/jats:underline>\n                        hodobacter\n                      <\/jats:italic>\n                      <jats:underline>n<\/jats:underline>\n                      itrogen-\n                      <jats:underline>f<\/jats:underline>\n                      ixation complex, commonly known as Rnf complex, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of this Rnf complex causes global defects in polymicrobial interaction, biofilm formation, cell growth and morphology, hydrogen sulfide production, and ATP synthesis. Targeted metabolomic profiling demonstrates that the loss of this respiratory enzyme significantly diminishes catabolism of numerous amino acids, which negatively impacts fusobacterial virulence as tested in a preterm birth model in mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01751-23","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T09:00:27Z","timestamp":1701939627000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["The respiratory enzyme complex Rnf is vital for metabolic adaptation and virulence in\n                    <i>Fusobacterium nucleatum<\/i>"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1264-7878","authenticated-orcid":true,"given":"Timmie A.","family":"Britton","sequence":"first","affiliation":[{"name":"Molecular Biology Institute, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5700-7188","authenticated-orcid":true,"given":"Chenggang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Molecular Genetics, University of Texas McGovern Medical School, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Oral &amp; Systemic Health Sciences, School of Dentistry, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Franklin","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Oral &amp; Systemic Health Sciences, School of Dentistry, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha I.","family":"Camacho","sequence":"additional","affiliation":[{"name":"Division of Oral &amp; Systemic Health Sciences, School of Dentistry, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Truc T.","family":"Luong","sequence":"additional","affiliation":[{"name":"Division of Oral &amp; Systemic Health Sciences, School of Dentistry, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asis","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Medicine, Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1611-0469","authenticated-orcid":true,"given":"Hung","family":"Ton-That","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute, University of California, Los Angeles, California, USA"},{"name":"Division of Oral &amp; Systemic Health Sciences, School of Dentistry, University of California, Los Angeles, California, USA"},{"name":"Department of Microbiology, Immunology &amp; Molecular Genetics, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00542-10"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-020-01801-y"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.10.3194-3203.1989"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.40.1.303-309.1983"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02838-14"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12248"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515593706"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0966-842x(02)00034-3"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.10.3204-3209.1989"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-015-0439-z"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2012.01889.x"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/20002297.2023.2165001"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01206-08"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00595"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16967-2"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abn4948"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.07.012"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.07.006"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110537"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201847638"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611567200"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00209-09"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06503.x"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2006482118"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01936-22"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00360-18"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00279903"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096696"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010318107"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2009.01871.x"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00219"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.12493"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711093105"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.5b00020"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg252"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01109-9"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpmc.104"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-010-0555-8"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00406-12"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302x.1990.tb00418.x"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2002.tb11373.x"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.048934-0"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.039180-0"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.051813-0"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.25.3.775-780.1979"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.173.2.900-902.1991"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01580-18"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2019.114699"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp356"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00710-w"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.01751-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.01751-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T10:42:38Z","timestamp":1705401758000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.01751-23"}},"subtitle":[],"editor":[{"given":"Indranil","family":"Biswas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Ozlem","family":"Yilmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,1,16]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1,16]]}},"alternative-id":["10.1128\/mbio.01751-23"],"URL":"https:\/\/doi.org\/10.1128\/mbio.01751-23","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,16]]},"assertion":[{"value":"2023-07-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01751-23"}}