Project: Identification of a Novel non-antibiotic Bactericidal agent to fight antimicrobial resistance

Acronym NOBACT (Reference Number: JPIAMR2022-059)
Duration 01/03/2023 - 28/02/2026
Project Topic To stem the ever-growing threat of antimicrobial resistance (AMR) our research focuses on non-antibiotic strategies to combat multi-drug resistant (MDR) pathogens. We have developed up to the preclinical stage an inhibitor, 3A11, which is the first targeting copper-transporting P-type ATPase protein CopA. It limits the growth of several Gram-positive pathogens, such as Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, including the two most common MDR strains causing nosocomial infections: methicillin-resistant S. aureus and vancomycin-resistant enterococci. We will collect sequenced clinical isolates from the vast bacterial repositories of the project partners to test the bactericidal potential of 3A11. The inclusion of clinical isolates with different phenotypes and genetic lineages will guide our investigations of the underlying molecular mechanisms of action. This will be further studied using transcriptomic analysis to determine changes in the global expression profiles of the isolates induced by 3A11. As part of the preclinical development, we will investigate the potential development of resistance to 3A11 by determining the mutation rates in the bacteria and further characterising the ensuing phenotypes, genotypes, and fitness cost. Lastly, as bacterial pathogenesis initiates in epithelial cells within the host, followed by bacterial uptake in macrophages, we will gauge the efficacy of 3A11 in epithelial cells like human keratinocytes (HaCaT), primary keratinocytes, human macrophage cells (THP-1), and in murine models.
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Call 2nd JPIAMR-ACTION Joint Call 2022

Project partner

Number Name Role Country
1 Karolinska Institutet Coordinator Sweden
2 University of Rennes 1 Partner France
3 Centre International de Recherche en Infectiologie Partner France
4 Maxel Consulting ApS Partner Denmark
5 Statens Serum Institut Partner Denmark