The Translocation‑Transfer project established a virtual research network that brought together experts from the IMI‑Translocation consortium, the EU‑OpenScreen infrastructure, and additional global partners such as the Pew Charitable Trust and the CO‑ADD initiative. Over a three‑year period (1 April 2019 to 30 June 2022) the network created a publicly accessible web portal (www.eu‑openscreen.eu/projects/translocation‑transfer/overview.html) that consolidates expertise, experimental data, and screening resources. The portal allows researchers to view the collective capabilities of the main players and to submit targeted queries, thereby accelerating knowledge transfer across the antibiotic discovery community.
Scientifically, the network focused on the fundamental barriers that limit antibiotic entry into Gram‑negative bacteria. A key outcome was the presentation by Timothy Schulz‑Utermoehl of a strategy to deliver RNAi‑based precision therapeutics by exploiting a selective TonB‑dependent transporter. The study demonstrated that engineered RNAi molecules could be taken up efficiently when coupled to a TonB ligand, thereby overcoming the outer‑membrane permeability hurdle that typically restricts nucleic‑acid therapeutics. Complementary work within the network addressed the permeability barrier from multiple angles: advanced molecular simulations revealed how porin dynamics influence small‑molecule transport; experimental assays quantified antibiotic accumulation using novel uptake‑reporting systems; and structural analyses of RND‑type efflux pumps identified binding pockets amenable to inhibition. Together, these efforts provided a mechanistic framework linking transporter expression, membrane composition, and drug uptake, and highlighted potential chemical substructures that enhance permeation into Gram‑negative pathogens.
Other technical contributions included the integration of CO‑ADD’s standardized MIC and killing‑rate data, which enabled systematic benchmarking of new compounds against an ESKAPE panel. The Pew‑Charitable Trust supplied a long‑term database for disseminating these results, ensuring that findings from the network remain accessible to the wider research community. The EU‑OpenScreen platform supplied high‑throughput screening capacity at 25 sites across eight European countries, allowing rapid evaluation of candidate molecules identified through the network’s collaborative efforts. Workshops and short‑talk sessions—held in Madrid, Hamburg, and other venues—fostered cross‑disciplinary dialogue, with participants presenting on topics ranging from efflux‑pump inhibition to the effect of external stimuli on outer‑membrane transporter expression.
Collaboration was structured around three stakeholder groups: (i) partners linked to the Translocation IMI consortium, (ii) EU‑OpenScreen sites, and (iii) broader AMR research communities. The project’s governance included a steering committee that coordinated the kick‑off workshop in Madrid on 2 April 2019, where representatives from Jacobs University, Fraunhofer, Basel, and other institutions outlined research priorities and established working groups. Despite operating without a dedicated budget, the network secured the necessary institutional approvals and leveraged existing infrastructure to minimize overhead. The IMI funding under the Innovative Medicines Initiative provided the financial backbone, while the absence of a direct budget for the network itself underscored the collaborative, resource‑sharing ethos that defined the project. Through these combined efforts, the Translocation‑Transfer initiative advanced both the scientific understanding of Gram‑negative permeability and the practical tools needed to translate that knowledge into new antibacterial agents.
