Fighting resistant bacteria and Global pandemics Marc LECUIT, MD PhD Biology of Infection Unit Institut Pasteur Paris, France This is a great pleasure to be here, and Id like to thnak the ERC and Professor Eva Kondorosi for her kind invitation. I am a clinician and scientist workinf in the field of Infectious diseases at Institut Pasteur and Necker Children’s hospital in Paris, France
Human therapies Traditional medicine Empirical Scientific medicine Salix alba Traditional medicine Empirical Scientific medicine Mechanistic studies → Highly effective and selective therapies Anticancer therapies HIV, HCV acetylsalicylic acid Historically, human therapies have been developed form traditional medicine…
Human therapies Traditional medicine Empirical Scientific medicine Salix alba Traditional medicine Empirical Scientific medicine Mechanistic studies → Highly effective and selective therapies Anticancer therapies HIV, HCV acetylsalicylic acid
Antimicrobials Germ theory of diseases → concept of infection “Bugs are bad” Antimicrobials Natural Synthetic As for antimicrobials, ReAct Group 2015
Antibiotics are extremely efficient Antibiotics target specifically bacterial products e.g. peptidoglycan (cell wall: ß-lactams, glycopeptides) openoregonstate.pressbooks.pub/microbiology
Antibiotics are extremely efficient Growth complete inhibition
But do not target microbial pathogens specifically… Impact on the microbiota The complex bacterial communities that inhabit our gut doi:10.1126/science.aaf5670
But do not target microbial pathogens specifically… Impact on the microbiota J Clin Invest. 2010;120(12):4332-4341
But do not target microbial pathogens specifically… Selection of resistant bacteria Mutations Transfer of resistance ReAct Group 2015
A need for a strategic and tactical change From weapons of mass destruction Shutterstock
A need for a strategic and tactical change From weapons of mass destruction To precision weapon → Tech-Connect
Develop highly selective and efficacious drugs Kill specifically the pathogen CRISPR-Cas Antimicrobial peptides Phages What can we do? CRISPR Cas: Gene editing
Develop highly selective and efficacious drugs Block pathogenic mechanisms Anti toxin Block type III secretion systems
Develop highly selective and efficacious drugs Host-directed therapy Block pathogenic mechanisms Anti toxin Block type III secretion systems
Develop highly selective and efficacious drugs Target antibiotic resistant bacteria CRISPR-Cas Bikard, Curr Opin Microbiol. 2017 Jun;37:155-160
A call for basic research Basic microbiology Host-pathogens interactions Microbial pathogenesis Host responses
A call for basic research in biology Nature 517, 369–372 OrthoMaM
A call for basic research in biology Nature 517, 369–372 OrthoMaM