{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:23:49Z","timestamp":1787009029851,"version":"build-2736575974"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Infections with Bacteroides fragilis are routinely treated with metronidazole, a 5-nitroimidazole antibiotic that is active against most anaerobic microorganisms. Metronidazole has remained a reliable treatment option, but resistance does occur, including in B. fragilis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In this study we tested whether haemin, a growth supplement for B. fragilis in vivo and in vitro, had an influence on the susceptibility of resistant B. fragilis strains to metronidazole. We further tested whether haemin-deprived B. fragilis would be more susceptible to oxygen and oxidative stress. Metronidazole has been described to cause oxidative stress, which we argued would be exacerbated in haemin-deprived B. fragilis because the bacteria harness haemin, and the iron released from it, in antioxidant enzymes such as catalase and superoxide dismutase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Haemin was omitted from growth media and the effect on metronidazole susceptibility was monitored in susceptible and resistant B. fragilis strains. Further, haemin-deprived B. fragilis were tested for resistance to aeration and hydrogen peroxide and the capacity for the removal of oxygen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Omission of haemin from the growth medium rendered metronidazole-resistant B. fragilis strains, including an MDR isolate from the UK, highly susceptible to metronidazole. Haemin deprivation further rendered B. fragilis highly susceptible to oxygen, which was further exacerbated in resistant strains. B. fragilis was incapable of scavenging oxygen when haemin was omitted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We propose that haemin deprivation overrules resistance mechanisms by rendering B. fragilis hypersusceptible to metronidazole due to a compromised antioxidant defence. Monitoring of haemin concentrations is imperative when conducting metronidazole susceptibility testing in B. fragilis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkab485","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T15:11:31Z","timestamp":1639667491000},"page":"1027-1031","source":"Crossref","is-referenced-by-count":10,"title":["Haemin deprivation renders\n                    <i>Bacteroides fragilis<\/i>\n                    hypersusceptible to metronidazole and cancels high-level metronidazole resistance"],"prefix":"10.1093","volume":"77","author":[{"given":"Ana","family":"Paunkov","sequence":"first","affiliation":[{"name":"Institute for Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Kinderspitalgasse 15, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Gutenbrunner","sequence":"additional","affiliation":[{"name":"Institute for Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Kinderspitalgasse 15, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"S\u00f3ki","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Faculty of Medicine, University of Szeged, Semmelweis 6, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Leitsch","sequence":"additional","affiliation":[{"name":"Institute for Specific Prophylaxis and Tropical Medicine Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Kinderspitalgasse 15, A-1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"key":"2022033111260433900_dkab485-B1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev.mi.38.100184.001453","article-title":"Bacteroides of the human lower intestinal tract","volume":"38","author":"Salyers","year":"1984","journal-title":"Annu Rev Microbiol"},{"key":"2022033111260433900_dkab485-B2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1128\/CMR.00008-07","article-title":"Bacteroides: the good, the bad, and the nitty-gritty","volume":"20","author":"Wexler","year":"2007","journal-title":"Clin Microbiol Rev"},{"key":"2022033111260433900_dkab485-B3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.anaerobe.2016.11.003","article-title":"Trends in antimicrobial resistance among Bacteroides species and Parabacteroides species in the United States from 2010-2012 with comparison to 2008\u20132009","volume":"43","author":"Snydman","year":"2017","journal-title":"Anaerobe"},{"key":"2022033111260433900_dkab485-B4","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.meegid.2018.06.020","article-title":"Mechanisms of Bacteroides fragilis resistance to metronidazole","volume":"64","author":"Ghotaslou","year":"2018","journal-title":"Infect Genet Evol"},{"key":"2022033111260433900_dkab485-B5","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.anaerobe.2018.10.004","article-title":"Metronidazole resistance and nim genes in anaerobes: a review","volume":"55","author":"Alauzet","year":"2019","journal-title":"Anaerobe"},{"key":"2022033111260433900_dkab485-B6","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1086\/428623","article-title":"Anaerobic sepsis due to multidrug-resistant Bacteroides fragilis: microbiological cure and clinical response with linezolid therapy","volume":"40","author":"Wareham","year":"2005","journal-title":"Clin Infect Dis"},{"key":"2022033111260433900_dkab485-B7","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1017\/S0031182017002025","article-title":"A review on metronidazole: an old warhorse in antimicrobial chemotherapy","volume":"146","author":"Leitsch","year":"2019","journal-title":"Parasitology"},{"key":"2022033111260433900_dkab485-B8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1574-6968.2011.02357.x","article-title":"In vitro activity of deferoxamine against Porphyromonas gingivalis","volume":"323","author":"Moon","year":"2011","journal-title":"FEMS Microbiol Lett"},{"key":"2022033111260433900_dkab485-B9","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1128\/jb.145.1.466-471.1981","article-title":"Influence of heme and vitamin B12 on growth and fermentations of Bacteroides species","volume":"145","author":"Chen","year":"1981","journal-title":"J Bacteriol"},{"key":"2022033111260433900_dkab485-B10","doi-asserted-by":"crossref","first-page":"6895","DOI":"10.1128\/jb.178.23.6895-6903.1996","article-title":"Oxidative stress response in an anaerobe, Bacteroides fragilis: a role for catalase in protection against hydrogen peroxide","volume":"178","author":"Rocha","year":"1996","journal-title":"J Bacteriol"},{"key":"2022033111260433900_dkab485-B11","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1099\/jmm.0.47242-0","article-title":"Coincidence of bft and cfiA genes in a multi-resistant clinical isolate of Bacteroides fragilis","volume":"56","author":"Terhes","year":"2007","journal-title":"J Med Microbiol"},{"key":"2022033111260433900_dkab485-B12","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0147-619X(89)90060-7","article-title":"Transferable 5-nitroimidazole resistance in the Bacteroides fragilis group","volume":"21","author":"Breuil","year":"1989","journal-title":"Plasmid"},{"key":"2022033111260433900_dkab485-B13","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1128\/AAC.38.5.1047","article-title":"Nucleotide sequence analysis of two 5-nitroimidazole resistance determinants from Bacteroides strains and of a new insertion sequence upstream of the two genes","volume":"38","author":"Haggoud","year":"1994","journal-title":"Antimicrob Agents Chemother"},{"key":"2022033111260433900_dkab485-B14","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000076954","article-title":"Molecular characterization of nitroimidazole resistance in metronidazole-resistant Bacteroides species isolated from hospital patients in Kuwait","volume":"13","author":"Jamal","year":"2004","journal-title":"Med Princ Pract"},{"key":"2022033111260433900_dkab485-B15","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1099\/jmm.0.05452-0","article-title":"Molecular characterization of imipenem-resistant, cfiA-positive Bacteroides fragilis isolates from the USA, Hungary and Kuwait","volume":"53","author":"S\u00f3ki","year":"2004","journal-title":"J Med Microbiol"},{"key":"2022033111260433900_dkab485-B16","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ijpddr.2021.04.004","article-title":"A reassessment of the role of oxygen scavenging enzymes in the emergence of metronidazole resistance in trichomonads","volume":"16","author":"Gehl","year":"2021","journal-title":"Int J Parasitol Drugs Drug Resist"},{"key":"2022033111260433900_dkab485-B17","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1111\/mmi.12438","article-title":"An anaerobic bacterium, Bacteroides thetaiotaomicron, uses a consortium of enzymes to scavenge hydrogen peroxide","volume":"90","author":"Mishra","year":"2013","journal-title":"Mol Microbiol"},{"key":"2022033111260433900_dkab485-B18","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/jac\/dkab097","article-title":"Haem is crucial for medium-dependent metronidazole resistance in clinical isolates of Clostridioides difficile","volume":"76","author":"Boekhoud","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"2022033111260433900_dkab485-B19","doi-asserted-by":"crossref","first-page":"e0058521","DOI":"10.1128\/JCM.00585-21","article-title":"The integrity of heme is essential for reproducible detection of metronidazole-resistant Clostridioides difficile by agar dilution susceptibility tests","volume":"59","author":"Wu","year":"2021","journal-title":"J Clin Microbiol"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/77\/4\/1027\/43192450\/dkab485.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/77\/4\/1027\/43192450\/dkab485.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T10:02:41Z","timestamp":1648720961000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/77\/4\/1027\/6510936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,19]]},"references-count":19,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,1,19]]},"published-print":{"date-parts":[[2022,3,31]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkab485","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4,1]]},"published":{"date-parts":[[2022,1,19]]}}}