title: Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.
abstract: Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa. Taurocholic acid (1) was isolated from the fermentation broth of the fish microbiome-derived strain of Rhodococcus erythropolis and identified using standard NMR and MS methods. Screening of the twelve predominant human steroidal bile acid components revealed that a subset of these compounds can inhibit biofilm formation, induce detachment of preformed biofilms under static conditions, and that these compounds display distinct structure-activity relationships against V. cholerae and P. aeruginosa. Our findings highlight the significance of distinct bile acid components in the regulation of biofilm formation and dispersion in two different clinically relevant bacterial pathogens, and suggest that the bile acids, which are endogenous mammalian metabolites used to solubilize dietary fats, may also play a role in maintaining host health against bacterial infection.
authors.affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Sanchez
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Cheng
authors.affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Warner
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.
authors.forename: Loni
authors.initials: L
authors.lastname: Townsley
authors.affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Peach
authors.affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarro
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shikuma
authors.affiliation: Chemical Screening Center, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Bray
authors.affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.
authors.forename: Romina M
authors.initials: RM
authors.lastname: Riener
authors.affiliation: Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.
authors.forename: Fitnat H
authors.initials: FH
authors.lastname: Yildiz
authors.affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, United States of America.|Department of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Linington
mesh_terms: D000818:Animals; D018441:Biofilms; D005399:Fishes / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000502:physiology*