Project Number: 8042-42000-007-00-D
Project Type: In-House Appropriated
Start Date: Jul 1, 2016
End Date: Jun 30, 2021
Objective 1: Develop protocols to isolate and identify bioactive compounds from agricultural products such as fruit peels and rinds. Objective 2: Investigate mode of action of bioactive compounds that are able to mitigate virulence in the gut (mouse model), or restrict environmental dissemination and survival of pathogens, utilizing metagenomic, transcriptomic and proteomic analyses. Sub-objective 2.1. Determine influence of bioactive compounds on pathogens during in vitro (i.e., biofilm formation, swarm motility, and survival in harsh environments such as low water activity and low pH) and ex vivo assays (i.e. invasion of cultured human intestinal cells). Sub-objective 2.2. Determine how bioactive compounds impact host microbiome and pathogens during infection in animal models by acquiring and interpreting genomic and transcriptomic data.
Objective 1: Several plant-derived bioactive compounds, from the non-edible portions of pomegranate, orange and avocado, have been detected and are currently being investigated for their antimicrobial activity. A more systematic approach will be adopted for screening bioactive compounds. To begin with screening protocols will be focused on evaluating pathogen responses under different conditions, including migration on wet surfaces, biofilm formation, survival in stressful environments (e.g. low pH and reduced water activity), and competitiveness in the gastrointestinal tract. We will investigate synergistic effects which might render antimicrobial resistant isolates sensitive to conventional antibiotics. Identification of such compounds will aid in developing environmentally compatible strategies to eliminate/control pathogens. Objective 2: We have previously documented that pomegranate peel extracts restrict Salmonella migration on wet surfaces by down-regulating the genes required for motility. We will examine if these extracts have potential to significantly restrict the infectivity of Citrobacter in the mouse gut (model system for enterohemorrhagic infections). Transcriptomics approaches will be utilized to determine the impact of bioactive compounds on virulence of pathogens inside and outside the host environment; while metagenomic profiling will be conducted to assess the impact of bioactive compounds on composition and competitiveness of host gut microflora on disease progression. Developing a better understanding of the mode of action of promising plant-derived bioactive compounds against food-borne pathogens will significantly aid in developing strategies to reduce antibiotic use.