Molecular profiling of tissue biopsies reveals unique signatures associated with streptococcal necrotizing soft

Robert Thänert1, Andreas Itzek1, Jörn Hoßmann1

  • 1Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany.

Nature Communications
|August 28, 2019
PubMed

Insights

Necrotizing soft tissue infections (NSTIs) are caused by single or multiple bacteria. This study reveals distinct pathogenic mechanisms and identifies host immune responses as potential diagnostic biomarkers for faster diagnosis and targeted therapies.

Area of Science:

  • Infectious Diseases
  • Microbiology
  • Immunology
  • Genomics

Background:

  • Necrotizing soft tissue infections (NSTIs) are severe bacterial infections with significant morbidity and mortality.
  • Understanding the distinct pathophysiological mechanisms of monomicrobial versus polymicrobial NSTIs is crucial for improved clinical management.
  • Current diagnostic and therapeutic strategies often lack specificity due to the heterogeneity of NSTI-causing pathogens.

Purpose of the Study:

  • To elucidate the distinct pathogenic mechanisms underlying monomicrobial (Streptococcus pyogenes) and polymicrobial NSTIs.
  • To investigate host and pathogen transcriptional responses in patient biopsies.
  • To identify potential host-derived diagnostic biomarkers for NSTIs.

Main Methods:

  • Integration of microbial community profiling (metagenomics) with host and pathogen transcriptional analysis (RNA-seq) on patient biopsies.
  • Comparative analysis of gene expression patterns in monomicrobial (S. pyogenes) and polymicrobial NSTIs.
  • Identification of key virulence factors and host immune response signatures.

Main Results:

  • Polymicrobial NSTIs exhibit pathogenicity driven by synergistic interactions among bacterial species, leading to inflammation and tissue destruction.
  • Monomicrobial S. pyogenes NSTIs are characterized by the expression of specific virulence factors.
  • A distinct interferon-related host response was identified specifically in S. pyogenes NSTIs, suggesting its potential as a diagnostic biomarker.

Conclusions:

  • Distinct molecular mechanisms differentiate monomicrobial and polymicrobial NSTIs, impacting disease progression.
  • Host-derived transcriptional signatures, particularly interferon responses, show promise for the specific diagnosis of S. pyogenes NSTIs.
  • This research provides critical insights for developing targeted diagnostic and therapeutic strategies for diverse NSTI types.

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