HDHL INTIMIC cofunded call “Interrelation of the Intestinal Microbiome, Diet and Health” (IM 2017)

The role of diet-dependent human microbiome encoded T3SS-dependent effectors in modulating health
DIME
2018-10-01
2021-09-30
Prof. Dr. Pascal Falter-Braun
Partner Organization Partner Country

1. Overall project description


1.1 Summary



Main objectives:


SA1 - Identification of effector proteins 


The effector-prediction resulated in a set of effectors already transfered to the experimental pipeline


SA2 - Microbiome-human interaction mapping


Pipeline started (s. below)


SA3 - relate human effector targets to functional and  disease modules


Theoretical groups are working on different aspects. Experiments will follow in a later sate of the project (according to time plane)


SA4 - Verification of human health


Results expected in the later state of the  project.


We are in the process of identifying T3SS and T4SS substrates from existing human microbiome datasets with a focus on microbes affected by diet.


WP In-silico analysis of reference genomes and effector prediction
Main criteria for the selection of 800 bona fide in-silico predicted effectors:
- availability of good quality genomes from public sources
 - availability of strain material
- strains isolated from human intestine
- type 3 secreted effectors


Results
77 (proteo-)bacterial strains genomes were found to be screened for T3SS. Taxonomic composition of the seleted strains consist of 57 gamma proteo bacterial strains, 7 beta proteo bacterial strains and 12 delta/epsiolon proteo bacterial strains.
The secretion system prediction for  the 77 strains revealed the following distributution: 15% T3SS, 10% T4SS, 29% T3SS and T3SS, and in 23% no secretion system could be found.
An intense performance comparison of tools based either on N- terminal features (EffectiveT3, DeepT3) or homologies (pEffect, ELD) has been carried out. An intrinsic disorder analysis was performed in order to support the predictions. The resulting scoring scheme was used for ranking of the predicted effectors. Analysis incl. scoring and post-processing (removal of flegellar and secretion system compounds) resulted in a set of 1,800 effectors for interactome analysis. 
Based on the computational analysis the experimental pipeline already started with the ordering of the respective biological material (bacterial DNA and bacterial strains) and primer design for effector cloning. Preliminary experiments with E. coli including optimization of primer and pcr and cultivation conditions are carried out in parallel. 


Expected project impact:


This project aims to shed light on functional and mechanistic questions basis of how microbes actively modulate the host as nutrition-mediated responses. An understanding of the mechanisms by which microbes can influence human molecular processes and ultimately human health will allow precise and informed health prevention and intervention strategies. 
Depending on the project results, informed nutritional intervention strategies can be developed to decrease disease risks. Disease modules overlapping with human effector targets can be alleviated by dietary or pharmaceutical interventions. Development of effector binding drugs, secretion system blockers or competitive antagonists may be an application scenario.


 





1.2 Highlights

Our results so far correspond to our project planning but are not yet at the stage where they can be communicated to the public as new insights.


To date our most important research results are the succesfull screening and effector predictions within 77 bacterial genomes  and constitution of a set of 1,800 predicted effectors. To our knowledge this result indicates for the first time the potential of bacterial proteins from non-pathogenic microbes in the microbiome that may directly influencing human intracellular processes. 


 


4. Impact


4.1 List of publications

AuthorsTitleYear, Issue, PPDoiPdf

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
MicrobiologistsFalter-Braun, Brun, RatteiPresentation

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

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