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A multiomics approach to identify host-microbe alterations associated with infection severity in diabetic foot
Michael Radzieta1,2, Fatemah Sadeghpour-Heravi3, Timothy J Peters4
1South Western Sydney Limb Preservation and Wound Research, South Western Sydney LHD, Sydney, Australia. M.Radzieta@westernsydney.edu.au.
Abstract:
Diabetic foot infections (DFIs) are a major cause of hospitalization and can lead to lower extremity amputation. In this pilot study, we used a multiomics approach to explore the host-microbe complex within DFIs. We observed minimal differences in the overall microbial composition between PEDIS infection severities, however Staphylococcus aureus and Streptococcus genera were abundant and highly active in most mild to moderate DFIs. Further, we identified the significant enrichment of several virulence factors associated with infection pathogenicity belonging to both Staphylococcus aureus and Streptococcus. In severe DFIs, patients demonstrated a greater microbial diversity and differential gene expression demonstrated the enrichment of multispecies virulence genes suggestive of a complex polymicrobial infection. The host response in patients with severe DFIs was also significantly different as compared to mild to moderate DFIs. This was attributed to the enrichment of host genes associated with inflammation, acute phase response, cell stress and broad immune-related responses, while those associated with wound healing and myogenesis were significantly depleted.
Insights
Diabetic foot infections show similar microbes but differing virulence factors and host responses across severity. Severe infections involve complex polymicrobial interactions and impaired healing.
Area of Science:
- Microbiology
- Genomics
- Immunology
Background:
- Diabetic foot infections (DFIs) are a significant cause of hospitalization and amputation.
- Understanding the host-microbe interactions in DFIs is crucial for effective treatment.
Purpose of the Study:
- To investigate the host-microbe complex in diabetic foot infections using a multiomics approach.
- To compare microbial and host responses across different diabetic foot infection severities.
Main Methods:
- Multiomics analysis of diabetic foot infection samples.
- Assessment of microbial composition and gene expression.
- Analysis of host immune response and cellular pathways.
Main Results:
- Minimal differences in overall microbial composition across infection severities.
- Abundant and active Staphylococcus aureus and Streptococcus genera in mild to moderate DFIs.
- Enrichment of virulence factors in Staphylococcus aureus and Streptococcus.
- Increased microbial diversity and polymicrobial virulence genes in severe DFIs.
- Distinct host response in severe DFIs, with enriched inflammation and immune genes, and depleted wound healing genes.
Conclusions:
- DFIs involve complex host-microbe interactions that vary with infection severity.
- Severe DFIs are characterized by polymicrobial infections and a dysregulated host response, impairing healing.
- Targeting virulence factors and modulating host immune responses may be crucial for treating severe DFIs.
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