{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:06:36Z","timestamp":1792807596497,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,9,30]],"date-time":"2017-09-30T00:00:00Z","timestamp":1506729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK076169"],"award-info":[{"award-number":["DK076169"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>One of the most common urologic problems afflicting millions of people worldwide is urinary tract infection (UTI). The severity of UTIs ranges from asymptomatic bacteriuria to acute cystitis, and in severe cases, pyelonephritis and urosepsis. The primary cause of UTIs is uropathogenic Escherichia coli (UPEC), for which current antibiotic therapies often fail. UPEC forms multicellular communities known as biofilms on urinary catheters, as well as on and within bladder epithelial cells. Biofilm formation protects UPEC from environmental conditions, antimicrobial therapy, and the host immune system. Previous studies have investigated UPEC biofilm formation in aerobic conditions (21% oxygen); however, urine oxygen tension is reduced (4\u20136%), and urine contains molecules that can be used by UPEC as alternative terminal electron acceptors (ATEAs) for respiration. This study was designed to determine whether these different terminal electron acceptors utilized by E. coli influence biofilm formation. A panel of 50 urine-associated E. coli isolates was tested for the ability to form biofilm under anaerobic conditions and in the presence of ATEAs. Biofilm production was reduced under all tested sub-atmospheric levels of oxygen, with the notable exception of 4% oxygen, the reported concentration of oxygen within the bladder.<\/jats:p>","DOI":"10.3390\/ijms18102077","type":"journal-article","created":{"date-parts":[[2017,10,2]],"date-time":"2017-10-02T13:10:05Z","timestamp":1506949805000},"page":"2077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Biofilm Formation by Uropathogenic Escherichia coli Is Favored under Oxygen Conditions That Mimic the Bladder Environment"],"prefix":"10.3390","volume":"18","author":[{"given":"Allison","family":"Eberly","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Floyd","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor","family":"Beebout","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer","family":"Colling","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Stratton","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4249-8997","authenticated-orcid":false,"given":"Maria","family":"Hadjifrangiskou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S1047-2797(00)00072-7","article-title":"Urinary tract infection: Self-reported incidence and associated costs","volume":"10","author":"Foxman","year":"2000","journal-title":"Ann. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/jhm.2079","article-title":"Estimating hospital costs of catheter-associated urinary tract infection","volume":"8","author":"Kennedy","year":"2013","journal-title":"J. Hosp. Med."},{"key":"ref_3","first-page":"1","article-title":"Ambulatory medical care utilization estimates for 2007","volume":"169","author":"Schappert","year":"2011","journal-title":"Vital Health Stat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.idc.2013.09.003","article-title":"Urinary tract infection syndromes: Occurrence, recurrence, bacteriology, risk factors, and disease burden","volume":"28","author":"Foxman","year":"2014","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"359","DOI":"10.12816\/0003256","article-title":"Recurrent Urinary Tract Infections Management in Women: A review","volume":"13","year":"2013","journal-title":"Sultan Qaboos Univ. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrurol.2010.190","article-title":"The epidemiology of urinary tract infection","volume":"7","author":"Foxman","year":"2010","journal-title":"Nat. Rev. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.molmed.2016.09.003","article-title":"Urinary Tract Infection: Pathogenesis and Outlook","volume":"22","author":"McLellan","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S1047-2797(02)00272-7","article-title":"Acute pyelonephritis in US hospitals in 1997: Hospitalization and in-hospital mortality","volume":"13","author":"Foxman","year":"2003","journal-title":"Ann. Epidemiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"519","DOI":"10.2217\/ahe.13.38","article-title":"Urinary tract infection in older adults","volume":"9","author":"Rowe","year":"2013","journal-title":"Aging Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e749","DOI":"10.1542\/peds.2011-1332","article-title":"Technical report\u2014Diagnosis and management of an initial UTI in febrile infants and young children","volume":"128","author":"Finnell","year":"2011","journal-title":"Pediatrics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e01191-16","DOI":"10.1128\/mBio.01191-16","article-title":"Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and blaNDM-5, Causing a Complicated Urinary Tract Infection in a Patient from the United States","volume":"7","author":"Mediavilla","year":"2016","journal-title":"MBio"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/nrurol.2015.199","article-title":"The emerging threat of multidrug-resistant Gram-negative bacteria in urology","volume":"12","author":"Zowawi","year":"2015","journal-title":"Nat. Rev. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1126\/science.1084550","article-title":"Intracellular bacterial biofilm-like pods in urinary tract infections","volume":"301","author":"Anderson","year":"2003","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rosen, D.A., Hooton, T.M., Stamm, W.E., Humphrey, P.A., and Hultgren, S.J. (2007). Detection of intracellular bacterial communities in human urinary tract infection. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040329"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1128\/IAI.00090-08","article-title":"Utilization of an intracellular bacterial community pathway in Klebsiella pneumoniae urinary tract infection and the effects of FimK on type 1 pilus expression","volume":"76","author":"Rosen","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.1073\/pnas.1601720113","article-title":"Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an extracellular niche to initiate bladder stone formation","volume":"113","author":"Schaffer","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrmicro2415","article-title":"The biofilm matrix","volume":"8","author":"Flemming","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3389\/fmicb.2011.00158","article-title":"Horizontal gene exchange in environmental microbiota","volume":"2","author":"Aminov","year":"2011","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"a010306","DOI":"10.1101\/cshperspect.a010306","article-title":"Bacterial biofilms: Development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era","volume":"3","author":"Kostakioti","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_20","first-page":"267","article-title":"Persister cells and the riddle of biofilm survival","volume":"70","author":"Lewis","year":"2005","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"184ra60","DOI":"10.1126\/scitranslmed.3005497","article-title":"Genomic diversity and fitness of E. coli strains recovered from the intestinal and urinary tracts of women with recurrent urinary tract infection","volume":"5","author":"Chen","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hagan, E.C., Lloyd, A.L., Rasko, D.A., Faerber, G.J., and Mobley, H.L. (2010). Escherichia coli global gene expression in urine from women with urinary tract infection. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001187"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/sj.ki.5002230","article-title":"Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney","volume":"72","author":"Lane","year":"2007","journal-title":"Kidney Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8922","DOI":"10.1073\/pnas.95.15.8922","article-title":"Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesin","volume":"95","author":"Sokurenko","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.tim.2004.11.006","article-title":"Biofilms: The matrix revisited","volume":"13","author":"Branda","year":"2005","journal-title":"Trends Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1128\/JB.01649-09","article-title":"Exopolysaccharides produced by Streptococcus mutans glucosyltransferases modulate the establishment of microcolonies within multispecies biofilms","volume":"192","author":"Koo","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1099\/jmm.0.46064-0","article-title":"Expression of cellulose and curli fimbriae by Escherichia coli isolated from the gastrointestinal tract","volume":"54","author":"Bokranz","year":"2005","journal-title":"J. Med. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1046\/j.1365-2958.2001.02337.x","article-title":"The multicellular morphotypes of Salmonella typhimurium and Escherichia coli produce cellulose as the second component of the extracellular matrix","volume":"39","author":"Zogaj","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1111\/j.1462-5822.2009.01323.x","article-title":"Evolving concepts in biofilm infections","volume":"11","author":"Stoodley","year":"2009","journal-title":"Cell. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1177\/0022034509359403","article-title":"Biofilm dispersal: Mechanisms, clinical implications, and potential therapeutic uses","volume":"89","author":"Kaplan","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7042","DOI":"10.1128\/IAI.70.12.7042-7049.2002","article-title":"Effect of trimethoprim-sulfamethoxazole on recurrent bacteriuria and bacterial persistence in mice infected with uropathogenic Escherichia coli","volume":"70","author":"Schilling","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/j.1574-6976.2012.00339.x","article-title":"Host-pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection","volume":"36","author":"Hannan","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1128\/IAI.69.7.4572-4579.2001","article-title":"Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection","volume":"69","author":"Mulvey","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/microbiolspec.MBP-0016-2015","article-title":"Metabolism and Fitness of Urinary Tract Pathogens","volume":"3","author":"Alteri","year":"2015","journal-title":"Microbiol. Spectr."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Alteri, C.J., Smith, S.N., and Mobley, H.L. (2009). Fitness of Escherichia coli during urinary tract infection requires gluconeogenesis and the TCA cycle. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000448"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1111\/j.1365-2958.2011.07660.x","article-title":"A central metabolic circuit controlled by QseC in pathogenic Escherichia coli","volume":"80","author":"Hadjifrangiskou","year":"2011","journal-title":"Mol. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0005-2728(97)00034-0","article-title":"Alternative respiratory pathways of Escherichia coli: Energetics and transcriptional regulation in response to electron acceptors","volume":"1320","author":"Unden","year":"1997","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1046\/j.1432-1327.1998.2510538.x","article-title":"Changes in the proton potential and the cellular energetics of Escherichia coli during growth by aerobic and anaerobic respiration or by fermentation","volume":"251","author":"Tran","year":"1998","journal-title":"Eur. J. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.1128\/JB.00030-16","article-title":"The UbiI (VisC) Aerobic Ubiquinone Synthase Is Required for Expression of Type 1 Pili, Biofilm Formation, and Pathogenesis in Uropathogenic Escherichia coli","volume":"198","author":"Floyd","year":"2016","journal-title":"J. Bacteriol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/j.acra.2008.04.013","article-title":"Urinary oxygen tension measurement in humans using magnetic resonance imaging","volume":"15","author":"Wang","year":"2008","journal-title":"Acad. Radiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1126\/science.282.5393.1494","article-title":"Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli","volume":"282","author":"Mulvey","year":"1998","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1111\/j.1462-5822.2007.00952.x","article-title":"Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili","volume":"9","author":"Wright","year":"2007","journal-title":"Cell. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Floyd, K.A., Moore, J.L., Eberly, A.R., Good, J.A., Shaffer, C.L., Zaver, H., Almqvist, F., Skaar, E.P., Caprioli, R.M., and Hadjifrangiskou, M. (2015). Adhesive fiber stratification in uropathogenic Escherichia coli biofilms unveils oxygen-mediated control of type 1 pili. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004697"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6195","DOI":"10.1128\/JB.01012-12","article-title":"Transposon mutagenesis identifies uropathogenic Escherichia coli biofilm factors","volume":"194","author":"Hadjifrangiskou","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17897","DOI":"10.1073\/pnas.0606795103","article-title":"Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria","volume":"103","author":"Pinkner","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Velasquez, M.T., Ramezani, A., Manal, A., and Raj, D.S. (2016). Trimethylamine N-Oxide: The Good, the Bad and the Unknown. Toxins, 8.","DOI":"10.3390\/toxins8110326"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1002\/1522-2683(200108)22:13<2763::AID-ELPS2763>3.0.CO;2-G","article-title":"Nitrite and nitrate measurement in human urine by capillary electrophoresis","volume":"22","author":"Morcos","year":"2001","journal-title":"Electrophoresis"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/BF00211416","article-title":"Clinical experience with multiagent intravesical therapy in interstitial cystitis patients unresponsive to single-agent therapy","volume":"11","author":"Ghoniem","year":"1993","journal-title":"World J. Urol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejogrb.2011.12.014","article-title":"Interstitial cystitis: Diagnosis and management","volume":"161","author":"Vij","year":"2012","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4586","DOI":"10.1073\/pnas.96.8.4586","article-title":"Noninvasive measurement of anatomic structure and intraluminal oxygenation in the gastrointestinal tract of living mice with spatial and spectral EPR imaging","volume":"96","author":"He","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1128\/JB.01523-07","article-title":"Identification of type 3 fimbriae in uropathogenic Escherichia coli reveals a role in biofilm formation","volume":"190","author":"Ong","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1046\/j.1365-2958.1998.00797.x","article-title":"Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signalling pathways: A genetic analysis","volume":"28","author":"Kolter","year":"1998","journal-title":"Mol. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e00820","DOI":"10.1128\/mBio.00820-15","article-title":"Human Urine Decreases Function and Expression of Type 1 Pili in Uropathogenic Escherichia coli","volume":"6","author":"Greene","year":"2015","journal-title":"MBio"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e02038","DOI":"10.1128\/mBio.02038-14","article-title":"Pilicide ec240 disrupts virulence circuits in uropathogenic Escherichia coli","volume":"5","author":"Greene","year":"2014","journal-title":"MBio"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e00645-13","DOI":"10.1128\/mBio.00645-13","article-title":"Escherichia coli Biofilms Have an Organized and Complex Extracellular Matrix Structure","volume":"4","author":"Hung","year":"2013","journal-title":"MBio"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nchembio.242","article-title":"Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation","volume":"5","author":"Cegelski","year":"2009","journal-title":"Nat. Chem. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/10\/2077\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:46:19Z","timestamp":1760208379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/10\/2077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,30]]},"references-count":56,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10]]}},"alternative-id":["ijms18102077"],"URL":"https:\/\/doi.org\/10.3390\/ijms18102077","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,30]]}}}