{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T19:02:23Z","timestamp":1783364543605,"version":"3.54.6"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011865","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000}}],"reference-count":99,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The role of bacteria in the etiology of dental caries is long established, while the role of fungi has only recently gained more attention. The microbial invasion of dentin in advanced caries especially merits additional research. We evaluated the fungal and bacterial community composition and spatial distribution within carious dentin. Amplicon 16S rRNA gene sequencing together with quantitative PCR was used to profile bacterial and fungal species in caries-free children (n = 43) and 4 stages of caries progression from children with severe early childhood caries (n = 32). Additionally, healthy (n = 10) and carious (n = 10) primary teeth were decalcified, sectioned, and stained with Grocott\u2019s methenamine silver, periodic acid Schiff (PAS) and calcofluor white (CW) for fungi. Immunolocalization was also performed using antibodies against fungal \u03b2-D-glucan, gram-positive bacterial lipoteichoic acid, gram-negative endotoxin,\n                    <jats:italic>Streptococcus mutans<\/jats:italic>\n                    , and\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    . We also performed field emission scanning electron microscopy (FESEM) to visualize fungi and bacteria within carious dentinal tubules. Bacterial communities observed included a high abundance of\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>mutans<\/jats:italic>\n                    and the\n                    <jats:italic>Veillonella parvula<\/jats:italic>\n                    group, as expected. There was a higher ratio of fungi to bacteria in dentin-involved lesions compared to less severe lesions with frequent preponderance of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    ,\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>dubliniensis<\/jats:italic>\n                    , and in one case\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>tropicalis<\/jats:italic>\n                    . Grocott\u2019s silver, PAS, CW and immunohistochemistry (IHC) demonstrated the presence of fungi within carious dentinal tubules. Multiplex IHC revealed that fungi, gram-negative, and gram-positive bacteria primarily occupied separate dentinal tubules, with rare instances of colocalization. Similar findings were observed with multiplex immunofluorescence using anti-\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>mutans<\/jats:italic>\n                    and anti-\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>albicans<\/jats:italic>\n                    antibodies. Electron microscopy showed monomorphic bacterial and fungal biofilms within distinct dentin tubules. We demonstrate a previously unrecognized phenomenon in which fungi and bacteria occupy distinct spatial niches within carious dentin and seldom co-colonize. The potential significance of this phenomenon in caries progression warrants further exploration.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011865","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T14:35:58Z","timestamp":1716906958000},"page":"e1011865","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Fungi and bacteria occupy distinct spatial niches within carious dentin"],"prefix":"10.1371","volume":"20","author":[{"given":"Rosalyn M.","family":"Sulyanto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2198-9124","authenticated-orcid":true,"given":"Clifford J.","family":"Beall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasey","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Montesano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Juang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahr B.","family":"Hashmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Bradbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene J.","family":"Leys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Edgerton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita P.","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann L.","family":"Griffen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"ppat.1011865.ref001","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3389\/fped.2017.00157","article-title":"Early Childhood Caries: Prevalence, Risk Factors, and Prevention.","volume":"5","author":"S Anil","year":"2017","journal-title":"Front Pediatr."},{"key":"ppat.1011865.ref002","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13005-020-00237-z","article-title":"Dental caries in primary and permanent teeth in children\u2019s worldwide, 1995 to 2019: a systematic review and meta-analysis.","volume":"16","author":"M Kazeminia","year":"2020","journal-title":"Head Face Med"},{"key":"ppat.1011865.ref003","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.adaj.2015.06.003","article-title":"Fifty-one million: A mythical number that matters.","volume":"146","author":"BL Edelstein","year":"2015","journal-title":"J Am Dent Assoc"},{"key":"ppat.1011865.ref004","first-page":"59","article-title":"Policy on Early Childhood Caries (ECC): Classifications, Consequences, and Preventive Strategies.","volume":"39","year":"2017","journal-title":"Pediatr Dent."},{"key":"ppat.1011865.ref005","doi-asserted-by":"crossref","first-page":"650","DOI":"10.14219\/jada.archive.2009.0250","article-title":"Beyond the dmft.","volume":"140","author":"PS Casamassimo","year":"2009","journal-title":"The Journal of the American Dental Association"},{"key":"ppat.1011865.ref006","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/ipd.12441","article-title":"Does oral health influence school performance and school attendance? 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