Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during Candida albicans-Associated Denture Stomatitis
Identifieur interne : 000430 ( Main/Exploration ); précédent : 000429; suivant : 000431Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during Candida albicans-Associated Denture Stomatitis
Auteurs : Junko Yano [États-Unis] ; Alika Yu [États-Unis] ; Paul L. Fidel [États-Unis] ; Mairi C. Noverr [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2016.
Abstract
Denture stomatitis (DS) is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. The disease is caused by
Url:
DOI: 10.1371/journal.pone.0159692
PubMed: 27453977
PubMed Central: 4959791
Affiliations:
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Transcription Factors Efg1 and Bcr1 Regulate Biofilm Formation and Virulence during <italic>Candida albicans</italic>
-Associated Denture Stomatitis</title>
<author><name sortKey="Yano, Junko" sort="Yano, Junko" uniqKey="Yano J" first="Junko" last="Yano">Junko Yano</name>
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<wicri:regionArea>Department of Oral and Craniofacial Biology, Dental School, Louisiana State University Health Sciences Center, New Orleans, Louisiana</wicri:regionArea>
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<author><name sortKey="Yu, Alika" sort="Yu, Alika" uniqKey="Yu A" first="Alika" last="Yu">Alika Yu</name>
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<wicri:regionArea>Department of Prosthodontics, Dental School, Louisiana State University Health Sciences Center, New Orleans, Louisiana</wicri:regionArea>
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<author><name sortKey="Fidel, Paul L" sort="Fidel, Paul L" uniqKey="Fidel P" first="Paul L." last="Fidel">Paul L. Fidel</name>
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<author><name sortKey="Noverr, Mairi C" sort="Noverr, Mairi C" uniqKey="Noverr M" first="Mairi C." last="Noverr">Mairi C. Noverr</name>
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<placeName><region type="state">Louisiane</region>
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<wicri:regionArea>Department of Prosthodontics, Dental School, Louisiana State University Health Sciences Center, New Orleans, Louisiana</wicri:regionArea>
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<front><div type="abstract" xml:lang="en"><p>Denture stomatitis (DS) is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. The disease is caused by <italic>Candida albicans</italic>
, which readily colonizes and form biofilms on denture materials. While evidence for biofilms on abiotic and biotic surfaces initiating <italic>Candida</italic>
infections is accumulating, a role for biofilms in DS remains unclear. Using an established model of DS in immunocompetent animals, the purpose of this study was to determine the role of biofilm formation in mucosal damage during pathogenesis using <italic>C</italic>
. <italic>albicans</italic>
or mutants defective in morphogenesis (<italic>efg1</italic>
<sup><italic>-/-</italic>
</sup>
) or biofilm formation (<italic>bcr1</italic>
<sup><italic>-/-</italic>
</sup>
<italic>)</italic>
. For <italic>in vivo</italic>
analyses, rats fitted with custom dentures, consisting of fixed and removable parts, were inoculated with wild-type <italic>C</italic>
. <italic>albicans</italic>
, mutants or reconstituted strains and monitored weekly for fungal burden (denture and palate), body weight and tissue damage (LDH) for up to 8 weeks. <italic>C</italic>
. <italic>albicans</italic>
wild-type and reconstituted mutants formed biofilms on dentures and palatal tissues under <italic>in vitro</italic>
, <italic>ex vivo</italic>
and <italic>in vivo</italic>
conditions as indicated by microscopy demonstrating robust biofilm architecture and extracellular matrix (ECM). In contrast, both <italic>efg1</italic>
<sup><italic>-/-</italic>
</sup>
and <italic>bcr1</italic>
<sup><italic>-/-</italic>
</sup>
mutants exhibited poor biofilm growth with little to no ECM. In addition, quantification of fungal burden showed reduced colonization throughout the infection period on dentures and palates of rats inoculated with <italic>efg1</italic>
<sup><italic>-/-</italic>
</sup>
, but not <italic>bcr1</italic>
<sup>-/-</sup>
, compared to controls. Finally, rats inoculated with <italic>efg1</italic>
<sup><italic>-/-</italic>
</sup>
and <italic>bcr1</italic>
<sup><italic>-/-</italic>
</sup>
mutants had minimal palatal tissue damage/weight loss while those inoculated with wild-type or reconstituted mutants showed evidence of tissue damage and exhibited stunted weight gain. These data suggest that biofilm formation is associated with tissue damage during DS and that Efg1 and Bcr1, both central regulators of virulence in <italic>C</italic>
. <italic>albicans</italic>
, have pivotal roles in pathogenesis of DS.</p>
</div>
</front>
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