Metagenomics and host-pathogen interactomics in diabetic foot infections

  • PD Dr. Eva Medina, Helmholtz Zentrum für Infektionsforschung, Braunschweig

Project Partners:
  • Prof. Dr. Trinad Chakraborty, Institut für medizinische Mikrobiologie, Universitätsklinikum Gießen und Marburg
  • PD Dr. Rolf Daniel, Institut für Mikrobiologie und Genetik, Georg-August-Universität Göttingen
  • Prof. Dr. Eugen Domann, Institut für medizinische Mikrobiologie, Universitätsklinikum Gießen und Marburg

The prevalence of diabetes mellitus worldwide has increased dramatically during the past few decades, and it is expected to increase even more in the future. As a result of the increase in diabetes, the comorbidities associated with the disease have also risen. Foot infections are the most common diabetes-related cause of hospitalization that very often results in amputation. The speed with which the DFI progresses, from a seemingly minor skin infection to a limb-threatening condition, reinforces the need for prompt diagnosis and treatment. Although generally, diagnosis is based on signs and symptoms of inflammation, accurate identification of infecting pathogens is paramount to reduce the spread of infection and decrease any unnecessary tissue loss. This is a complex task since diabetic foot infections (DFI) are usually polymicrobial and chronic infections may host biofilm bacteria not adequately detected by current microbiological testing. To deal with this complexity, a metagenomic approach will be used in this consortium to determine the impact of the microbial diversity and bioburden in the progression of DFI. This approach will be also used to evaluate the potential contribution of the skin microbiome to DIF. The most common and serious complication of DFI is osteomyelitis that can results in progressive inflammatory destruction of bones. Osteomyelitis is present in approximately 20% of cases of DFI and greatly increases the likelihood that the patient will require extremity amputation. Staphylococcus aureus is the most common cause of osteomyelitis in DFI patients. Diabetic foot osteomyelitis is often refractory to antibiotic treatment, a problem exacerbated by the increasing level of antibiotic-resistance among S. aureus clinical isolates as well as by the emergence of particularly persistent antibiotic-resistant clones during infection. Staphylococcal bone infections are thus likely to be a continuing and probably increasing problem in diabetic patients and an understanding of the interactions of this pathogen with bones is central to development of novel therapeutic strategies required to treat these increasingly antibiotic-resistant and persistent infections. To achieve a comprehensive understanding of the host-pathogen interactions during bone infection, it is also contemplated in this consortium to determine global host-pathogen transcriptome changes that occur during staphylococcal bone infection. The combine use of bacterial and host transcriptome to study the same infected tissue will reveal the dialogue between pathogen and host in a gene-by-gene and site- and time-specific manner. The final goal is to identify which bacterial transcripts influences host gene expression or vice versa (interactome). Overall, this consortium will provide valuable information that can be used to improve the diagnosis, prevention and treatment of DFI and its long-term complications.

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