JPIAMR 14th Call Partner Search Tool

General Information

• Type: Partner looking for project
• Organisation: University of strasbourg, CNRS
• Country: France (FR)

Research area

• Scientific area(s) of the call:
  1. Improvement of drug/plant protection agent efficacy and/or specificity through chemical modifications (including hit to lead optimisation)
  2. Design and implementation of new strategies (including optimisation of drug doses) for improved application, efficacy and delivery of single or combinations of antimicrobials
• One Health Setting:

  Human Health

• Type of studies/experimental approaches:

  in silico, in vitro, in vivo

• Keywords:

  antibiotic vectorisation; Trojan horse; Pseudomonas; siderophore; iron uptake

• Brief description of your expertise / expertise you are looking for:

  We have a longstanding expertise in antibiotic vectorization by siderophores, in siderophores chemistry and biology, in the molecular mechanisms involved in the uptake of siderophore-iron and siderophore-antibiotic-iron complexes into bacteria and in the mechanisms regulating the expression of the different iron uptake pathways. We have also an excellent expertise of Pseudomonas aeruginosa and have a large strain collection of mutants of P. aeruginosa, especially with mutations in the different siderophore-iron transporters.

• Brief description of your project / the project you would like to join:

  One of the difficulties in antibiotic development is the ability of the drugs to enter bacteria. The use of nutrient-importation pathways as gateways for the uptake of antibiotics has often been proposed to bypass the low permeability of the Gram-negative cell wall. Iron is an essential nutrient for bacteria growth, and to get access to it, microorganisms synthesize siderophores, small organic iron chelators. Antibiotics can be covalently linked to siderophores with the idea they will be transported into the pathogens during the ferri-siderophore uptake process – referred to as a Trojan-horse strategy. One such siderophore-antibiotic conjugate (Cefiderocol), is currently on the market and demonstrates that this strategy is working. A major bottleneck limiting the development of siderophore-antibiotic conjugates is the knowledge concerning the molecular mechanisms involved in the uptake of such compounds and the regulating network involved in the expression of bacterial siderophore-dependent iron pathways. We have the expertise to evaluate the ability of siderophore-antibiotic conjugates to enter bacteria efficiently and to evaluate the phenotypic adaptation of bacteria in the presence of such compounds.

Isabelle SCHALK

• Organisation: University of strasbourg, CNRS
• Position: Group leader
• E-mail: schalk@unistra.fr
• Web: bsc.unistra.fr/en/research-teams/team-schalkmislin/presentation/