title: Microbially mediated O-methylation of bisphenol A results in metabolites with increased toxicity to the developing zebrafish (Danio rerio) embryo.
abstract: Bisphenol A (BPA) is used in the manufacture of plastics, and has been identified in various environmental matrices, including human serum and breast milk. The prevalence of BPA in the environment and the potential exposure to humans underscores the need to more fully understand the fate of BPA in the environment and the resulting effects and toxicity to humans and other organisms. Here we demonstrate that Mycobacterium species, including Mycobacterium vanbaalenii strain PYR-1, are able to O-methylate BPA to its mono- and dimethyl ether derivatives (BPA MME and BPA DME, respectively). The O-methylation of BPA results in metabolites with increased toxicity as shown from differences in survival and occurrence of developmental lesions in developing zebrafish embryos exposed to BPA, BPA MME, and BPA DME. The mono- and dimethyl ether derivatives were more toxic than BPA, resulting in increased mortality at 5 (LC(50) = 0.66 and 1.2 mg L(-1)) and 28 (LC(50) = 0.38, <0.5 mg L(-1)) days post fertilization. Furthermore, exposure to either of the O-methylated metabolites resulted in an increase in the incidence of developmental lesions as compared to BPA exposure. These data illustrate a new mechanism for microbial transformation of BPA, producing metabolites warranting further study to understand their prevalence and effects in the environment.
authors.affiliation: Department of Biochemistry and Microbiology, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, United States.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: McCormick
authors.forename: Theo
authors.initials: T
authors.lastname: Van Es
authors.forename: Keith R
authors.initials: KR
authors.lastname: Cooper
authors.forename: Lori A
authors.initials: LA
authors.lastname: White
authors.forename: Max M
authors.initials: MM
authors.lastname: Häggblom
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D001673:Biodegradation, Environmental / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004781:Environmental Exposure / Q000032:analysis; D006801:Humans; D013058:Mass Spectrometry; D008738:Methyl Ethers / Q000633:toxicity; D008745:Methylation / Q000187:drug effects; D009161:Mycobacterium / Q000187:drug effects / Q000378:metabolism*; D010636:Phenols / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D016019:Survival Analysis; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D008738:Methyl Ethers; D010636:Phenols; C033413:dimethyl ether; C006780:bisphenol A; D000098826:Bisphenol A Compounds