Beta-Antithrombin as target for drug development

Each year more than 670.000 patients in Europe are infected with antibiotic resistant bacterial pathogens. 33.000 of these patients do not respond to clinical treatments and do not survive. In particular the increasing numbers of hospital-acquired infections pose a serious threat to patient health as these infectious are often caused by antibiotic resistant bacteria. In December 2019 we published an article in Nature Microbiology showing that an isoform of antithrombin (bAT), a human blood-borne inhibitor of the coagulation system, has bactericidal activity. In addition, we found bAT dampens inflammatory reactions and leads to improved survival in mice infected with an otherwise lethal dose of Escherichia coli bacteria. To test whether bAT is a target for the development of novel antibacterial therapies a consortium consisting of researchers from Lund University and Octapharma AB has been formed. This team will analyze whether bAT can serve as drug target by employing different preclinical and clinical approaches. To this end, in vitro, ex vivo, and in vivo models will be established that will be used to study the ability of bAT to clear an infection and reverse pathological immune reactions in response to infection with antibiotic resistant pathogens. The concept presented in this application describes an approach for the development of novel antimicrobial therapies that can be employed to treat patients suffering from infectious caused by antibiotic resistant bacteria.