title: Candida albicans stimulates Streptococcus mutans microcolony development via cross-kingdom biofilm-derived metabolites.
abstract: Candida albicans is frequently detected with heavy infection of Streptococcus mutans in plaque-biofilms from children affected with early-childhood caries, a prevalent and costly oral disease. The presence of C. albicans enhances S. mutans growth within biofilms, yet the chemical interactions associated with bacterial accumulation remain unclear. Thus, this study was conducted to investigate how microbial products from this cross-kingdom association modulate S. mutans build-up in biofilms. Our data revealed that bacterial-fungal derived conditioned medium (BF-CM) significantly increased the growth of S. mutans and altered biofilm 3D-architecture in a dose-dependent manner, resulting in enlarged and densely packed bacterial cell-clusters (microcolonies). Intriguingly, BF-CM induced S. mutans gtfBC expression (responsible for Gtf exoenzymes production), enhancing Gtf activity essential for microcolony development. Using a recently developed nanoculture system, the data demonstrated simultaneous microcolony growth and gtfB activation in situ by BF-CM. Further metabolites/chromatographic analyses of BF-CM revealed elevated amounts of formate and the presence of Candida-derived farnesol, which is commonly known to exhibit antibacterial activity. Unexpectedly, at the levels detected (25-50 μM), farnesol enhanced S. mutans-biofilm cell growth, microcolony development, and Gtf activity akin to BF-CM bioactivity. Altogether, the data provide new insights on how extracellular microbial products from cross-kingdom interactions stimulate the accumulation of a bacterial pathogen within biofilms.
authors.affiliation: Biofilm Research Laboratory, Department of Orthodontics and Divisions of Pediatric Dentistry &Community Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Dongyeop
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Systems Pharmacology &Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Arjun
authors.initials: A
authors.lastname: Sengupta
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Tagbo H R
authors.initials: TH
authors.lastname: Niepa
authors.affiliation: Department of Food Science, Gachon University, Seongnam, South Korea.
authors.forename: Byung-Hoo
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Systems Pharmacology &Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Aalim
authors.initials: A
authors.lastname: Weljie
authors.affiliation: Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Veronica S
authors.initials: VS
authors.lastname: Freitas-Blanco
authors.affiliation: Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: Ramiro M
authors.initials: RM
authors.lastname: Murata
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Stebe
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Daeyeon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Biofilm Research Laboratory, Department of Orthodontics and Divisions of Pediatric Dentistry &Community Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Hyun
authors.initials: H
authors.lastname: Koo
mesh_terms: D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology*; D015169:Colony Count, Microbial; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005204:Farnesol / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D005964:Glucosyltransferases / Q000378:metabolism; D055442:Metabolome; D044085:Microfluidics; D053758:Nanoparticles / Q000737:chemistry; D010539:Permeability; D013295:Streptococcus mutans / Q000187:drug effects / Q000254:growth & development*
chemical_list: D017077:Culture Media, Conditioned; D005204:Farnesol; D005964:Glucosyltransferases