Bacteriostatic mode of action of plant sesquiterpenes on the human microbial pathogen Helicobacter pylori and microbial communities of the gut

Lead Research Organisation: Institute of Food Research
Department Name: Contracts

Abstract

Sesquiterpenes are a structurally diverse family of plant natural products, prevalent among the solanaceous plants that are common in the diet such as tomatoes, potatoes, and peppers. While these compounds play critical roles in mediating ecological interactions between plants, insects and microbes, they also provide a rich source of high-value bioactives for human uses ranging from antibiotics, anticancer and anti-inflammatory agents, to flavours and fragrances. Though we ingest sesquiterpenes from dietary sources, little is known about how these compounds affect human microbes and microbial communities and the chemical ecology of the human gut. This gap in our knowledge will be addressed in the ISP. Initially, we will focus on a detailed mode of action study of capsidiol, an isoprenoid from peppers, and its bacteriostatic effect on the gut microbe Helicobacter pylori. These investigations will expand to consider the effects of capsidiol and related isoprenoid compounds on the gut microbial communities more broadly. To date, we have successfully isolated capsidiol from peppers, established several strains of H. pylori in the lab and conducted growth curve measurements. Additionally, we have evaluated the growth inhibitory activities of alpha-copaene from potatoes. The establishment of this experimental system and the successful pilot studies set the stage for metabolomics and transcriptomics studies to elucidate the manner in which isoprenoids in the diet perturb microbial metabolic function and gene expression. Subsequent studies will compare the action of a range of dietary (constitutive) sesquiterpenes, including alpha-copaene from potato varieties in collaboration with SCRI. Following targeted studies with H. pylori, we seek to study the effect of individual and mixtures of dietary phytochemicals on communities of commensal gut microorgansms, through close interactions with the IFR Gut ISP.

Publications

10 25 50
 
Description We have discovered how a widely used antibiotic works (mode of action) from studies with human pathogens. This discovery will enable the safe and effective use of this antibiotic and help in the development of novel drugs.
Exploitation Route This result will be put to work by clinicians, who armed with the fundamental knowledge of our discovery, will be able to identify people that are at risk of severe side effects from antibiotic use. Also, knowledge of the mode of action can be used to develop more potent formulations of the drug.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description We have made recent discoveries regarding the mode of action of antibiotics that allow us to make these drugs more safe and effective. We have filed a patent and are seeking commercial partners to move this forward into the public sector.
Sector Chemicals,Pharmaceuticals and Medical Biotechnology
Impact Types Societal

 
Title metabolomics data of plant and human pathogens exposed to biologically active compounds 
Description our investigations into the mode of action of plant and human antimicrobial compounds used metabolomics as a front line tool. in brief, we took metabolic snap shots following the exposure of pathogens to compounds. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact the results of these studies will be submitted in a manuscript in preparation 
 
Description Expert panelist, Metabolomics workshop. The Ohio State University, Columbus, OH, USA 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact I served as an expert panellist to discuss the application of metabolomics for biomedical science. my presentation stimulated much discussion.
Year(s) Of Engagement Activity 2014
 
Description IFR open day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact This activity was an open house for members of the public to learn more about research at the IFR. I presented a poster detailing our research.
Year(s) Of Engagement Activity 2012
 
Description Invited lecture, Academia Sinica, Institute of Biological Chemistry, Taipei, Taiwan 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact his was an international conference on our group's discoveries in terpene biosynthesis and the mechanism of action of plant antimicrobial compounds. my presentation stimulated much discussion and led to new collaborative opportunities.
Year(s) Of Engagement Activity 2014
 
Description Invited lecture, Agbiome, Durham, NC, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact this invited lecture provided the opportunity to share our group's recent discoveries in biocatalysis and bioactivity of plant antimicrobial compounds. my presentation stimulated much discussion and led to new collaborative opportunities.
Year(s) Of Engagement Activity 2015
URL http://www.agbiome.com
 
Description Invited lecture, Joint Bioenergy Institute, Emeryville, CA, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact this invited lecture provided the opportunity to share our groups recent discoveries in biocatalysts and bioactivity. my presentation stimulated much discussion and led to new collaborative opportunities.
Year(s) Of Engagement Activity 2015
URL http://www.jbei.org
 
Description Invited lecture, Metabolon, Durham, NC, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact this invited lecture provided the opportunity to share our group's recent discoveries in biocatalysis and bioactivity of plant antimicrobial compounds. my presentation stimulated much discussion and led to new collaborative opportunities.
Year(s) Of Engagement Activity 2015
URL http://www.metabolon.com
 
Description Invited lecture, The Ohio State University, Columbus, OH, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact this was an international conference on our group's discoveries in terpene biosynthesis and the mechanism of action of plant antimicrobial compounds. my presentation stimulated much discussion and led to new collaborative opportunities.
Year(s) Of Engagement Activity 2015
 
Description Invited lecture, University of California, Santa Cruz, Santa Cruz, CA, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact this was an international conference on our group's discoveries in terpene biosynthesis and the mechanism of action of plant antimicrobial compounds. my presentation stimulated much discussion and led to new collaborative opportunities.
Year(s) Of Engagement Activity 2015
 
Description Selected presentation, BBSRC Institutes Conference. Edinburgh, Scotland, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact this invited lecture provided the opportunity to share our group's recent discoveries of the mode of action of antibiotics. my presentation stimulated much discussion and led to new collaborative opportunities.
Year(s) Of Engagement Activity 2013