In this project the Martin and Luirink groups will unite to tackle the problem of antibiotic resistance using a range of experimental approaches. The project is supported by the private partners Fundación Medina, Bioversys AG and Pepscan. Also, the group of Seino Jongkees (AIMMS, VU) will be involved with their RaPID selection system of macrocyclic peptides. Employing innovative high-throughput screening and state of the art chemical biology selection methods, novel antibiotic compounds will be identified. Notably, the focus of this research is on finding antibiotics that interfere with the activity of a bacterial outer membrane protein known as BamA. While the activity of BamA is essential for Gram-negative bacteria, at present there are no clinically used antibiotics that function by inhibiting its activity. This approach has the potential to provide much-needed new antibiotics against the most critical pathogens listed on the World Health Organization’s recently published priority pathogens list, namely drug-resistant strains of Acinetobacter, Pseudomonas, and various Enterobacteriaceae (including Klebsiella and E. coli). In response, the research to be performed in this 4-year program will deliver innovative, first-in-class, Gram-negative specific antibiotics as leads for further development along with key insights into their working mechanisms.
Next Generation Antibiotics Targeting Gram-Negative Pathogens
26 February 2022
NWO-TTW (open technology programme) grant awarded to Nathaniel Martin (LUMC) and Joen Luirink (AIMMS, VU)