{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:43:45Z","timestamp":1793317425998,"version":"4.5.0"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI078972"],"award-info":[{"award-number":["AI078972"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI114800"],"award-info":[{"award-number":["AI114800"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI7271-24"],"award-info":[{"award-number":["T32AI7271-24"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"HHS | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["T32DE14318-10"],"award-info":[{"award-number":["T32DE14318-10"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Streptococcus pneumoniae<\/jats:named-content>\n            is an opportunistic pathogen that colonizes the nasopharynx. Herein we show that carbon availability is distinct between the nasopharynx and bloodstream of adult humans: glucose is absent from the nasopharynx, whereas galactose is abundant. We demonstrate that pneumococcal neuraminidase A (NanA), which cleaves terminal sialic acid residues from host glycoproteins, exposed galactose on the surface of septal epithelial cells, thereby increasing its availability during colonization. We observed that\n            <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n            mutants deficient in NanA and \u03b2-galactosidase A (BgaA) failed to form biofilms\n            <jats:italic>in vivo<\/jats:italic>\n            despite normal biofilm-forming abilities\n            <jats:italic>in vitro<\/jats:italic>\n            . Subsequently, we observed that glucose, sucrose, and fructose were inhibitory for biofilm formation, whereas galactose, lactose, and low concentrations of sialic acid were permissive. Together these findings suggested that the genes involved in biofilm formation were under some form of carbon catabolite repression (CCR), a regulatory network in which genes involved in the uptake and metabolism of less-preferred sugars are silenced during growth with preferred sugars. Supporting this notion, we observed that a mutant deficient in pyruvate oxidase, which converts pyruvate to acetyl-phosphate under non-CCR-inducing growth conditions, was unable to form biofilms. Subsequent comparative transcriptome sequencing (RNA-seq) analyses of planktonic and biofilm-grown pneumococci showed that metabolic pathways involving the conversion of pyruvate to acetyl-phosphate and subsequently leading to fatty acid biosynthesis were consistently upregulated during diverse biofilm growth conditions. We conclude that carbon availability in the nasopharynx impacts pneumococcal biofilm formation\n            <jats:italic>in vivo<\/jats:italic>\n            . Additionally, biofilm formation involves metabolic pathways not previously appreciated to play an important role.\n          <\/jats:p>","DOI":"10.1128\/iai.00277-16","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T03:05:13Z","timestamp":1470107113000},"page":"2922-2932","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":66,"title":["Neuraminidase A-Exposed Galactose Promotes Streptococcus pneumoniae Biofilm Formation during Colonization"],"prefix":"10.1128","volume":"84","author":[{"given":"Krystle A.","family":"Blanchette","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anukul T.","family":"Shenoy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Jeffrey","family":"Milner","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan P.","family":"Gilley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"McClure","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia A.","family":"Hinojosa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean C.","family":"Daugherty","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke J.","family":"Tallon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Ott","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"King","sequence":"additional","affiliation":[{"name":"Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA"},{"name":"Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Tettelin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos J.","family":"Orihuela","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)00938-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.medin.2015.07.005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60549-1"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/528688"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/505710"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555816537.ch9"},{"key":"e_1_3_3_8_2","first-page":"93","article-title":"Pneumococcal vaccines. WHO position paper","volume":"82","author":"World Health Organization","year":"2007","unstructured":"World Health Organization. 2007. Pneumococcal vaccines. WHO position paper. Wkly Epidemiol Rec. 82:93\u2013104.","journal-title":"Wkly Epidemiol Rec."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1704.101115"},{"key":"e_1_3_3_10_2","first-page":"1","article-title":"Deaths: preliminary data for 2009","volume":"59","author":"Kochanek KD","year":"2011","unstructured":"Kochanek KD, Xu J, Murphy SL, Minino AM, Kung HC. 2011. Deaths: preliminary data for 2009. Natl Vital Stat Rep 59:1\u201351.","journal-title":"Natl Vital Stat Rep"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1402692"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5409.1837"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5418.1318"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.296.2.202"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2009.05.016"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00488-12"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/MLG.0b013e31806009b0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000161346.30752.18"},{"key":"e_1_3_3_19_2","first-page":"251","article-title":"Bacterial evasion of antimicrobial peptides by biofilm formation","volume":"306","author":"Otto M","year":"2006","unstructured":"Otto M. 2006. Bacterial evasion of antimicrobial peptides by biofilm formation. Curr Top Microbiol Immunol 306:251\u2013258.","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.11.010"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01310-13"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00200-12"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00673-06"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061217"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.70.9.5244-5251.2004"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00309-11"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026707"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01131-10"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1996.425954.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00745-13"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00228-09"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1086\/598483"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00425-08"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00832-10"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1080\/00016480260000111"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01251-07"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04984.x"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01125-09"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201212-2277OC"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.35"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.3791\/50115"},{"key":"e_1_3_3_42_2","volume-title":"Guide for the care and use of laboratory animals","author":"National Research Council","year":"2011","unstructured":"National Research Council. 2011. Guide for the care and use of laboratory animals, 8th ed. National Academies Press, Washington, DC.","edition":"8"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01148-06"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-7-80"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.24.8463-8471.2004"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.2144\/000112531"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-10-r106"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-161"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt285"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2012.08.008"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-12-200"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.15.5376-5386.2005"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00499-15"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05290-11"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.11.7775-7778.2005"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.921-924.2000"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2041-1014.2012.00658.x"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.045609-0"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026587"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00438-13"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028738"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00268-12"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090974"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.24.8340-8349.2005"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.12.3406-3410.2002"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.6.1951-1957.2003"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12102"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-1956-8"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201400363"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01781-14"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.11.011"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13228"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00277-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00277-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T10:07:50Z","timestamp":1646474870000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00277-16"}},"subtitle":[],"editor":[{"given":"A.","family":"Camilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":74,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1128\/IAI.00277-16"],"URL":"https:\/\/doi.org\/10.1128\/iai.00277-16","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"2016-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}