The 5th course is scheduled October 16-24, 2021
Director

P. Courvalin (Institut Pasteur)

Scientific advisors

M. Gilmore (Harvard Medical School), G. Wright (McMaster University)

Scientific committee

G. Challis, T. Dougherty, E. Duffy, D. Hughes, S. Lahiri, F. Lebreton, S. Lory, A. Myers, S. Projan, J. Rex, H.‑G. Sahl, M.‑W. Tan, U. Theuretzbacher

Organizing commitee

C. Grillot-Courvalin, B. Pansier

The specific goal of ICARe is to bring leaders in academics and industry
together with trained scientists at the dawn of their careers.

Objective

The emergence and spread of bacteria resistant to many drug classes seriously threaten all branches of modern medicine. There is a growing gap in the first-hand experience and deep knowledge of antibiotic discovery and resistance. The goal of ICARe is to bring leaders in academics and industry together with trained scientists at the dawn of their careers to bridge this gap. State-of-the-art approaches in antibiotic discovery and the impact and mechanisms of resistance will be examined.

Course

The faculty comprises 40 internationally recognized scientists and physicians who have made significant contributions to antibiotic development, infectious diseases, and resistance management. Faculty members are in residence for a minimum of two days for informal interactions with students. Graduates will emerge with a state-of-the-art understanding of the antibiotics in clinical use, their modes of action, and resistance mechanisms. Furthermore, the course covers modern antibiotic discovery approaches, including appropriate chemical matter and libraries, advancing hits to leads, and the application of next-generation nucleic acid-based technologies for drug discovery and resistance detection. The course aims to build an international cadre of collaborative, well networked, and highly trained specialists.

Audience

ICARe is designed for assistant professors, post-doctoral and ID fellows, senior Ph.D. students, and scientists from the diagnostic, biotech, and pharmaceutical industries, either working in or contemplating entering the field of antibiotics. Decision-makers involved in the discovery, development, and approval of new antibiotics and in elaborating programs for better stewardship of antibiotics and mitigation of resistance from both the public and private sectors will also benefit. Attendance is limited to 40 students.

Selection criteria

Participants will be selected by the Scientific Committee that will ensure that the participants reflect the global nature of the problem with a special attention to gender equality, educational background, involvement in the field of antibiotics (research projects, scientific or industrial, which could be presented during the course are welcome), and decision-making responsibility in the finding of new antibiotics and of their appropriate use.

Format

The course will be administered over 9 days and will consist of formal instruction and hands-on bioinformatics.

Application: April 15th – August 7th, 2021.

Program outline

Antibiotic resistance and discovery

  • Antibiotic resistance is a global and medical problem
  • Overview of antibiotic R&D: history and strategies
  • The socio-economic challenges of antibiotic discovery

Modes of action and mechanisms of resistance of existing classes

  • Cell wall: Structure, synthesis, and targets
  • Outer- and Inner-membrane: Structure and function
  • Penicillin-binding proteins, beta-lactams, beta-lactamases and inhibitors
  • Glyco-lipopeptides
  • Ribosome:
    • Structure and function
    • Antibiotics active against the large subunit
    • Antibiotics active against the small subunit
  • Inhibitors of metabolism
  • Nucleic acid synthesis, replication, transcription: Inhibitors of type II topoisomerases, rifampicin, fidaxomicin
  • Efflux: structure-function of efflux systems and inhibitors
  • Influx-Efflux in P. aeruginosa
  • Cationic peptides

Origin, mutations, & transfer of resistance

  • Origins of resistance genes
  • Mutations, selection, biological cost, compensation
  • Mobile genetic elements

​​Antibiotic discovery

  • Antibiotic chemical space in Gram-positives and -negatives
  • Antibiotic chemical matter: Natural products, synthetics
  • New approaches in natural products discovery
  • Screens, hit generation, and hit to lead
  • Systems biology to guide antibiotic discovery and mode of action

Antibiotic development and approval​

  • Preclinical PK/PD and optimizing leads
  • Preclinical toxicity assessment
  • Pathways to approval and commercialization
  • New pathways to antibiotic registration

Strategies for more focused applications of antibiotics

  • Targeting biofilm, virulence, site-specific delivery
  • Antibiotic combinations and adjuvants
  • Antibiotics under development

Susceptibility determination and identification of resistance mechanisms

  • Antibiogram: phenotypic techniques and clinical categorization
  • Rapid techniques and point-of-care diagnostics
  • Diagnostic stewardship: Optimizing the treatment of infections
  • Mass spectrometry

New anti-infective strategies

  • Antibodies and engineered antibodies, vaccines, bacteriophages
  • Microbiome and antibiotics

Bioinformatics

  • Genomic epidemiology of MDR pathogens
  • Next-Generation Sequencing (NGS) in clinical microbiology
  • Mining genomes for resistance genes or biosynthetic gene clusters
  • Hands-on: A starter toolset for NGS-based analysis of MDR pathogens (optional)
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