Antimicrobial resistance (AMR) is now a major global public health threat. This clinical burden is associated with soaring treatment and societal costs with the yearly charge of AMR being estimated at around € 1.5 Billion and 25000 deaths in Europe (ECDC/EMEA “time to react”). Despite the recognized need for new antimicrobials for clinical use, the reality is that only two new classes of antibiotics have been brought to market in the last 30 years and many drug developers have left the field. This urgency is especially true when considering resistant Gram-negative infections where carbapenem-resistance is rising and use of drugs of last resort, such as colistin, is increasing. The New Drugs 4 Bad Bugs (ND4BB) initiative is a series of programmes designed to directly address some of the scientific challenges associated with antibacterial drug discovery and development. The over-arching concept of ND4BB is to create an innovative public-private collaborative partnership that will positively impact all aspects of AMR research with benefit on the future discovery and development of novel agents for the treatment, prevention and management of patients with bacterial infections.

Concept of the Translocation Programme:

The overall goals of the Translocation consortium are to:

1) increase the understanding on the overall permeability of drugs into Gram-negative bacteria; and 2) increase efficiency in antibiotic R&D through knowledge and data sharing and analysis of the combined package of information.

We will address both the discovery and informatics challenges associated with the goals above with a two tiered consortium. The discovery group is made up of renowned academics and SMEs from across Europe with the diverse expertise ranging from clinical microbiology to condensed matter physics needed to undertake this ambitious programme. This group, coupled with additional expertise from within the EFPIA partners, will bring an unrivalled focus and breadth of judgement to this important area of research. The efficiency group is also made up of experts from academia, SMEs, and industry, will work to bring a renewed interest in antibacterial research by coordinating the disclosure and combined analysis of previously confidential information, primarily from participating EFPIA companies, on historical successes and failures in antibacterial R&D. In addition, this group will help coordinate the dissemination of information and learnings from this and all other Topics initiated under the ND4BB programme.

The first one focused primarily on the discovery aspect:

• assays to study penetration and efflux in multi-resistant Gram-negative pathogens;
• an increased understanding of the impact of porin structure and intrinsic permeability;
• an increased understanding of hijacking bacterial transport mechanisms;
• an increased understanding of the use membrane permeability and the ability of adjunct molecules to improve the penetration of co-administered antimicrobials;
• an increased understanding of penetration and efflux via modelling and simulation;

while the second one is on the efficiency aspect:

• an information hub to manage information flow throughout and beyond the life of ND4BB;
• recommendations and best practices for all phases of antibacterial R&D.