SFB 1583: Decisions in Infectious Diseases (DECIDE)

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The global emergence of multidrug-resistant bacteria and pandemics, such as the COVID-19 pandemic caused by the novel SARS-CoV-2 coronavirus, fundamentally impact our health systems and societies. While pathogen-directed therapies have been very successful in combating infectious diseases, they provoke the evolution of microbes resistant to treatment and thereby force the pharmaceutical industry to constantly develop new classes of antimicrobial agents. The arms race between the development of new resistances and the approval of new effective antimicrobials seems to be already decided in favour of the microbes. In addition, the host immune response contributes to the fatal outcome of numerous infectious diseases, for example COVID-19. Therefore, fighting the pathogen alone does not have a sufficient therapeutic effect. These realities demand a rethinking of current therapeutic approaches towards strategies that focus on pathogen-triggered host responses and not the pathogen itself. While this approach has the potential to be superior to conventional microbe-oriented strategies, to date we know very little about possible host targets. Especially the processes that convert an initially harmless infection into severe or chronic disease have not been studied in a coordinated manner. Therefore, there is an urgent need to identify decision points within the host that govern infectious disease processes. Once recognised, these can be harnessed for future therapeutic interventions. In the collaborative research centre DECIDE (DECisions in Infectious DisEases) we propose to investigate three key decisions that determine the clinical outcome and severity of infections: (1) the initial pathogen contact to established infection; (2) the transition to a persistent infection; and (3) initiation of systemic spreading. These decisions are defined by a complex interplay of the pathogen with host barrier tissues and their commensal microbiota as well as local and systemic immune responses. We anticipate that the molecular events that underlie these interactions represent targets for intervention. Due to recent advances in cutting-edge single-cell technologies, complex human tissue and animal models and pathogen genetics, the course of infections can now be analysed in unprecedented molecular detail. Long-standing expertise on a repertoire of pathogens allows the investigators of DECIDE to explore interactions between these microbes, the host mucosal tissue and the immune system, as well as the microbiota in a unique multi-layered systems approach. Thereby, we aim to identify overarching common and pathogen-specific principles that will inform novel strategies for preventing and treating infectious diseases. It is our vision to create maximum synergy among the investigators of DECIDE in order to accomplish our mission to identify molecular decision points in infection processes and to exploit these as a new basis for anti-infective therapies.