Research

MTAvsAMR: new MultiTargeting Antibiotics against AntiMicrobial Resistance

Code:

J1-3030

Range:

01. October 2021 - 30. September 2024

Range:

1,57 FTE

Leader:

Lucija Peterlin Mašič

Field:

1-09 Natural sciences and Mathematics - Pharmacy

Abstract:

There is an urgent need for new therapies and new antibiotics to treat deadly infections caused by so-called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species), which are often resistant to available antibiotics. Antimicrobial resistance (AMR) is becoming an increasingly urgent public health threat in both clinical and community settings. One promising strategy to address this rapid evolution of resistance is the design of antimicrobial compounds equipotently inhibit two bacterial targets. The rationale for this approach is that the development of resistance to multitargeting antibiotics (MTA) would require the simultaneous occurrence of multiple specific mutations at both targets, which is extremely rare. In the MTAvsAMR (new MultiTargeting Antibiotics against AntiMicrobial Resistance) research project, we aim to develop a new structural class of MTA against two well-established molecular targets with innovative approaches to potent and safe multitargeting antibiotics with limited resistance. We will target the antibacterial activity of the new molecules against ESKAPE pathogens to address an unmet medical need, with a target product profile of methicillin-resistant (MRSA), vancomycin-intermediate (VISA) Staphylococcus aureus and Acinetobacter baumannii clinical isolates. To overcome the limitations of the current multitargeting antibiotics and to drive further development, we have established an interdisciplinary consortium to address fundamental questions related to the design of new antibacterial compounds with limited resistance, suitable PADMET properties, and lower susceptibility to efflux mechanisms. Excellent facilities combined with some of the latest technologies and expertise (DIvERGE, electrophysiology, channel mutagenesis and molecular dynamics simulations) will support MTA optimization. The MTAvsAMR project will evaluate compounds in original PADMET platform, which is unique for an academic setting and one of the key benefits of the research project. This multidisciplinary project has a strong interest in commercialization.