title: Anaerobic bacteria grow within Candida albicans biofilms and induce biofilm formation in suspension cultures.
abstract: The human microbiome contains diverse microorganisms, which share and compete for the same environmental niches. A major microbial growth form in the human body is the biofilm state, where tightly packed bacterial, archaeal, and fungal cells must cooperate and/or compete for resources in order to survive. We examined mixed biofilms composed of the major fungal species of the gut microbiome, Candida albicans, and each of five prevalent bacterial gastrointestinal inhabitants: Bacteroides fragilis, Clostridium perfringens, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. We observed that biofilms formed by C. albicans provide a hypoxic microenvironment that supports the growth of two anaerobic bacteria, even when cultured in ambient oxic conditions that are normally toxic to the bacteria. We also found that coculture with bacteria in biofilms induces massive gene expression changes in C. albicans, including upregulation of WOR1, which encodes a transcription regulator that controls a phenotypic switch in C. albicans, from the "white" cell type to the "opaque" cell type. Finally, we observed that in suspension cultures, C. perfringens induces aggregation of C. albicans into "mini-biofilms," which allow C. perfringens cells to survive in a normally toxic environment. This work indicates that bacteria and C. albicans interactions modulate the local chemistry of their environment in multiple ways to create niches favorable to their growth and survival.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, 600 16(th) Street, San Francisco, CA 94158, USA; Tetrad Program, Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16(th) Street, San Francisco, CA 94158, USA.
authors.forename: Emily P
authors.initials: EP
authors.lastname: Fox
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, 147-75, 1200 East California Boulevard, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, 147-75, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Elise S
authors.initials: ES
authors.lastname: Cowley
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, 600 16(th) Street, San Francisco, CA 94158, USA; School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA.
authors.forename: Clarissa J
authors.initials: CJ
authors.lastname: Nobile
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, 600 16(th) Street, San Francisco, CA 94158, USA.
authors.forename: Nairi
authors.initials: N
authors.lastname: Hartooni
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, 147-75, 1200 East California Boulevard, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, 147-75, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Dianne K
authors.initials: DK
authors.lastname: Newman
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, 600 16(th) Street, San Francisco, CA 94158, USA. Electronic address: ajohnson@cgl.ucsf.edu.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Johnson
mesh_terms: D000693:Anaerobiosis; D001421:Bacteria, Anaerobic / Q000145:classification / Q000502:physiology*; D018441:Biofilms / Q000254:growth & development*; D002176:Candida albicans / Q000502:physiology*; D018920:Coculture Techniques; D008828:Microbiological Techniques