title: Cellular Components Mediating Coadherence of Candida albicans and Fusobacterium nucleatum.
abstract: Candida albicans is an opportunistic fungal pathogen found as part of the normal oral flora. It can be coisolated with Fusobacterium nucleatum, an opportunistic bacterial pathogen, from oral disease sites, such as those involved in refractory periodontitis and pulp necrosis. The physical coadherence between these 2 clinically important microbes has been well documented and suggested to play a role in facilitating their oral colonization and colocalization and contributing to polymicrobial pathogenesis. Previous studies indicated that the physical interaction between C. albicans and F. nucleatum was mediated by the carbohydrate components on the surface of C. albicans and the protein components on the Fusobaterium cell surface. However, the identities of the components involved still remain elusive. This study was aimed at identifying the genetic determinants involved in coaggregation between the 2 species. By screening a C. albicans SN152 mutant library and a panel of F. nucleatum 23726 outer membrane protein mutants, we identified FLO9, which encodes a putative adhesin-like cell wall mannoprotein of C. albicans and radD, an arginine-inhibitable adhesin-encoding gene in F. nucleatum that is involved in interspecies coadherence. Consistent with these findings, we demonstrated that the strong coaggregation between wild-type F. nucleatum 23726 and C. albicans SN152 in an in vitro assay could be greatly inhibited by arginine and mannose. Our study also suggested a complex multifaceted mechanism underlying physical interaction between C. albicans and F. nucleatum and for the first time revealed the identity of major genetic components involved in mediating the coaggregation. These observations provide useful knowledge for developing new targeted treatments for disrupting interactions between these 2 clinically relevant pathogens.
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wu
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Cen
authors.affiliation: C3 Jian, Inc., Marina del Rey, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Kaplan
authors.affiliation: West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Lux
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Shi
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA, USA xhe@g.ucla.edu.
authors.forename: X
authors.initials: X
authors.lastname: He
mesh_terms: D001120:Arginine / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects / Q000502:physiology*; D018441:Biofilms; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology*; D002180:Candidiasis, Oral / Q000382:microbiology; D060085:Coinfection; D005674:Fusobacterium Infections / Q000382:microbiology; D016967:Fusobacterium nucleatum / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008358:Mannose / Q000494:pharmacology
chemical_list: D001120:Arginine; D008358:Mannose
keywords: adhesin; coaggregation; interspecies interaction; mannoprotein; opportunistic pathogen; oral microbiota