*MICHEL G. BERGERON

Selectomics to monitor and predict the emergence of resistance to antibiotics by using the human microbiome

Challenge: Antibiotics represent some of the most important drugs available to modern medicine because they can often treat bacterial infections that would otherwise pose a serious health threat. However, there is currently a lack of new antibiotic development by the industry due to reduced economic incentives as well as challenging scientific and regulatory requirements. To exacerbate the problem, bacteria targeted by existing agents have continued to evolve and have developed resistance to several antibiotics which limits the ability to effectively treat certain bacterial infections.

Solution: The team has developed genomic tools to determine how antibiotic exposure alters the human gut ecosystem and may trigger the emergence of antibiotic-resistant pathogens upon transfer of genes from the normal gut bacteria to such pathogens. Fecal flora from 18 healthy individuals exposed to antibiotics was collected and members of the aerobic and anaerobic communities of microbes were cultured. The metagenome of both cultured and uncultured gut microbiota was analyzed (close to 1,600 billion nucleotides) to identify genes (1,760 sequence types) and mobile genetic elements (2,895 sequence types) involved in antibiotic resistance. The research team also derived 2,760 gut microbiota cultures which can be used to screen, isolate, and characterize bacterial species that are resistant to antibiotic drugs early in support of drug development research.

Achievements/Impact: The results demonstrated the importance of the gut microflora in antibiotic resistance and in understanding the effects of antibiotics on the microbiota. These 1.5 trillion nucleotides data set is now included in an accessible data package that facilitates human microbiome inter-study comparisons. Quantifying the presence of resistance genes and mobile genetic elements, identifying new resistance genes, monitoring and predicting the resistance of new drugs, and assessing the activity of antibiotic compounds against a wide spectrum of resistance determinants, will ultimately enable the development of new and more potent antimicrobial treatments. Moreover, the methods and tools developed by the team will serve for other therapeutic interventions as in the future, regulatory agencies will require assessing the impact of all new drugs on the human microbiota.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Principal Investigator:


Michel G. Bergeron
CHU de Québec-
Université Laval

Co-investigators

Jacques Corbeil,
Marc Ouellette,
Paul H. Roy,
Sylvie Trottier

CHU de Québec-
Université Laval

Marc-Christian Domingo
INSPQ

Maurice Boissinot
GenePOC

Completed Project
$ 2,000,000 / 3 years
Supported by CQDM through:
• AstraZeneca
• Merck
• Pfizer
• MEI
• BL-NCE
 
And by a co-funding partner:
• Mitacs