Medical needs in the face of rising antibiotic resistance

Infections with Neisseria gonorrhoeae, the causative agent of gonorrhoea, are on the rise worldwide and represent a growing public health problem. Of particular concern is the increasing development of resistance to existing antibiotics, which can lead to treatment failure, prolonged illness and serious complications. Amongst others, these include infertility, miscarriages and an increased risk of HIV transmission.

In addition to the health consequences, there are considerable economic burdens. The World Health Organisation (WHO) estimates the global costs of treatment and lost productivity at several billion US dollars per year.

Against this backdrop, the NTSC-2 project pursues the further development of the novel antibiotic candidate Darobactin, which is effective against Gram-negative bacteria. Gonococcal infections are also caused by Gram-negative bacteria, which are characterised by an additional outer cell membrane and are therefore often particularly difficult to treat. The aim is to develop a new treatment option specifically for gonococcal infections.

Optimisation of a new antibiotic and preclinical validation

The focus of the work is to improve the oral bioavailability of Darobactin, i.e., the active substance’s ability to enter the bloodstream in sufficient quantities after oral administration. This is to be achieved through semi-synthetic modifications and so-called prodrug approaches, in which the active substance is initially administered in a precursor form and is only converted into its active form within the body. In parallel, a preclinical proof-of-concept study is conducted in a mouse model of gonococcal infection of the lower genital tract to investigate the efficacy of Darobactin following systemic administration (e.g. via injection).

This joint project is organised on the basis of a division of tasks. The Helmholtz Centre for Infection Research (HZI) and the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) are responsible for coordinating active substance production, microbiological investigations and ADME studies (absorption, distribution, metabolism, excretion). Leibniz University Hannover is responsible for the semi-synthetic development and the investigation of the in vitro safety profile.

The project aims to advance preclinical development into later clinical and regulatory phases and to facilitate subsequent translation into industrial application.

To learn more about funded GO-Bio projects, visit the overview page.