The microbial world is hugely diverse owing to its 3.7 billion years of evolution, which provides for both the opportunity of undiscovered metabolic capacity, including that for pollutant degradation, and the challenge of detecting, recovering, and characterizing this activity. While microbes have been exposed to small amounts of dioxins over millennia due to natural events such as forest fires, it is only in the last century or so that dioxins have become an abundant food source in nature due to anthropogenic activity. This may explain why there are only a few well characterized microbial strains with the ability to mineralize dioxins. We propose to characterize the microbial response to dioxins in pure cultures and microbial communities to understand the limitations on environmental detoxification of this hazardous class of compounds. Our long term goal is to develop microbes for enhanced biodegradation, to identify molecular markers to aid in site assessment, and to develop models for prediction of biodegradation at contaminated sites.
Our Specific Aims i n the present proposal are: (1) to elucidate the physiology, biochemistry, and genetics of chlorinated dioxins degradation in order to understand and improve the remediation of these highly toxic pollutants, (2) to assess (meta)genome-wide responses and metabolic capabilities by conducting physiogenomic studies of microorganisms and active microbial communities in response to chlorinated dioxins including those from environmentally important geosorbents, and (3) to explore and recover nature's catalytic diversity with the goal of developing a comprehensive profile of microbial community metabolic capabilities for degradation and/or mineralization of chlorinated dioxins and dioxin-like compounds in the environment. We propose to use enrichments to help identify the functionally active populations and hence genes, to use stable isotope probing to recover DNA from the active degrading populations, to use metagenomic and metatranscriptomic libraries and the novel technology of massive parallel RNA bait capture of target DNA and RNA to recover the full genes and operons, to use this information to understand the biochemistry of dioxins degradation, and to use transcriptomic and biochemical analyses of a model dioxin degrading bacterium to understand the total response of the organism to the various pressures involved during the degradation process (i.e. substrate and metabolite toxicity, metabolic fluxes, etc.).

Public Health Relevance

Knowledge of microbial chlorodioxins biodegradation can be exploited for remediation efforts to reduce human exposure to this hazardous class of compounds. Geosorbant materials play a natural role in capturing and slowing the movement of chlorodioxins making the microbial response to these matrices important for remediating these environmental repositories. The microbial response to chlorodioxins in the environment is a measurement of bioavailability and can be quantified as a risk factor for higher organisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES004911-23
Application #
8695355
Study Section
Special Emphasis Panel (ZES1-LWJ-D)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
23
Fiscal Year
2014
Total Cost
$480,328
Indirect Cost
$72,768
Name
Michigan State University
Department
Type
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Stedtfeld, Robert D; Stedtfeld, Tiffany M; Waseem, Hassen et al. (2017) Isothermal assay targeting class 1 integrase gene for environmental surveillance of antibiotic resistance markers. J Environ Manage 198:213-220
Fader, Kelly A; Nault, Rance; Zhang, Chen et al. (2017) 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism. Sci Rep 7:5921
Waseem, Hassan; Williams, Maggie R; Stedtfeld, Tiffany et al. (2017) Virulence factor activity relationships (VFARs): a bioinformatics perspective. Environ Sci Process Impacts 19:247-260
Fader, Kelly A; Nault, Rance; Kirby, Mathew P et al. (2017) Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERB?/? activation in aryl hydrocarbon receptor-elicited hepatotoxicity. Toxicol Appl Pharmacol 321:1-17
Kovalova, Natalia; Nault, Rance; Crawford, Robert et al. (2017) Comparative analysis of TCDD-induced AhR-mediated gene expression in human, mouse and rat primary B cells. Toxicol Appl Pharmacol 316:95-106
Samhan, Farag A; Stedtfeld, Tiffany M; Waseem, Hassan et al. (2017) On-filter direct amplification of Legionella pneumophila for rapid assessment of its abundance and viability. Water Res 121:162-170
Li, Jinpeng; Bhattacharya, Sudin; Zhou, Jiajun et al. (2017) Aryl Hydrocarbon Receptor Activation Suppresses EBF1 and PAX5 and Impairs Human B Lymphopoiesis. J Immunol 199:3504-3515
Stedtfeld, Robert D; Brett Sallach, J; Crawford, Robert B et al. (2017) TCDD administered on activated carbon eliminates bioavailability and subsequent shifts to a key murine gut commensal. Appl Microbiol Biotechnol 101:7409-7415
Dornbos, Peter; LaPres, John J (2017) Incorporating population-level genetic variability within laboratory models in toxicology: From the individual to the population. Toxicology 395:1-8
Ahmad, Farhan; Stedtfeld, Robert D; Waseem, Hassan et al. (2017) Most probable number - loop mediated isothermal amplification (MPN-LAMP) for quantifying waterborne pathogens in <25min. J Microbiol Methods 132:27-33

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