Improving Outcome of Necrotizing Fasciitis: Elucidation of Complex Host and Pathogen Signatures that Dictate Severity of Tissue Infection

The overall goal with INFECT is to advance our understanding of the pathophysiological mechanisms, prognosis, and diagnosis of the multifactorial highly lethal NSTIs. The fulminant course of NSTIs (in the order of hours) demands immediate diagnosis and adequate interventions in order to salvage lives and limbs. However, diagnosis and management are difficult due to heterogeneity in clinical presentation, in co-morbidities and in microbiological aetiology. Thus, there is an urgent need for novel diagnostic and therapeutic strategies in order to improve outcome of NSTIs. To achieve this, a comprehensive and integrated knowledge of diagnostic features, causative microbial agent, treatment strategies, and pathogenic mechanisms (host and bacterial disease traits and their underlying interaction network) is required. INFECT is designed to obtain such insights through an integrated systems biology approach in patients and different clinically relevant experimental models. Specific objectives of INFECT are to: 1. Unravel specific mechanisms underlying diseases signatures though a bottom-up systems approach applied to clinically relevant experimental settings 2. Apply a top-down systems biology approach to NSTI patient samples to pin-point key host and pathogen factors involved in the onset and development of infection 3. Identify and quantify disease signatures and underlying networks that contribute to disease outcome 4. Exploit identified disease traits for the innovation of optimized diagnostic tools 5. Translate the advanced knowledge generated into evidence-based guidelines for classification and management, and novel therapeutic strategies We have gathered a team of multidisciplinary researchers, clinicians, SMEs and a patient organization, each with a unique expertise, technical platform and/or model systems that together provide the means to successfully conduct the multifaceted research proposed and efficiently disseminate/exploit the knowledge obtained.