Antimicrobial resistance

Antimicrobial resistance is dramatically increasing worldwide and is becoming one of the most urgent public health threats. There is an urgent need for actions to reverse the curve of antimicrobial resistance dissemination and to develop innovative drugs (antibiotics, antiparasitic, antifungals, antivirals, antivectors) and therapeutic strategies for safer and sustainable treatments of infectious diseases. To respond to this urgency, the Institut Pasteur strategic plan fosters cutting edge projects to tackle antimicrobial resistance by incorporating clinical and field data within molecular, chemical, genetic and physiological approaches.

The global rise in antimicrobial resistance means that we are at risk of heading towards a post-antibiotic era, where common infections once again become life threatening. This dire prediction has raised awareness at the highest levels, including the United Nations and the G20. Therapy escape and the need for more effective treatments are not restricted to bacteria; they concern all microorganisms (viruses, fungi and parasites) and their vectors. Challenges include the emergence of resistance of the malaria parasite Plasmodium falciparum to artemisinin, the most effective treatment, and mosquitoes’ ability to change their behavior to counter insecticides.

AIMS

To improve understanding of resistance emergence and dissemination by combining approaches involving epidemiology, genomics, statistics, evolutionary biology, structural biology, chemical biology and modeling to identify factors contributing to the spread of resistant strains and resistance genes.
To analyze the physiology, ecology and evolution of microorganisms and their vectors. The molecular mechanisms governing microbial growth, metabolism and acquisition of resistance will be studied. For example, structural and chemical biology allow to characterize the mode of action of resistance at the molecular level. The complex interactions between the host and communities of microorganisms need to be taken into account to understand resistance. We aim at analyzing the formation of complex structures (e.g. biofilms) and the processes of quiescence, dormancy, persistence and tolerance, which represent additional means of treatment escape.
To identify new drugs and therapeutic strategies in response to antimicrobial resistance. We are synthetizing focused chemical libraries and exploring new targets, as those involved in host-microbe interaction and in the life cycle of the infectious agents. Phenotypic and molecular screening are implemented to identify selective inhibitors, phage therapy is further explored and diverse environments are exploited to find new natural products. In parallel, we aim at novel vaccines and immunotherapies to target microbes and resistant strains.

MEASURES

Recruit two five-year research groups (G5s)/research units.
Propose research funding that encourages novel synergistic and interdisciplinary approaches for the development of new treatments and alternative strategies to tackle infections.
Adopt metabolomics analysis techniques to examine microbes and their hosts.
Build a collaborative network of clinicians and public health experts.
Involve research units in the International Network in research on resistance.
Foster public-private partnerships for diagnostics and antimicrobial drug development.