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

Robert Thänert, Andreas Itzek, Jörn Hoßmann, Domenica Hamisch, Martin Bruun Madsen, Ole Hyldegaard, Steinar Skrede, Trond Bruun, Anna Norrby-Teglund, Eva Medina and Dietmar H. Pieper ()
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Robert Thänert: Helmholtz Center for Infection Research
Andreas Itzek: Helmholtz Center for Infection Research
Jörn Hoßmann: Helmholtz Center for Infection Research
Domenica Hamisch: Helmholtz Center for Infection Research
Martin Bruun Madsen: Copenhagen University Hospital, Rigshospitalet
Ole Hyldegaard: Copenhagen University Hospital, Rigshospitalet
Steinar Skrede: Haukeland University Hospital
Trond Bruun: Haukeland University Hospital
Anna Norrby-Teglund: Karolinska University Hospital
Eva Medina: Helmholtz Center for Infection Research
Dietmar H. Pieper: Helmholtz Center for Infection Research

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Necrotizing soft tissue infections (NSTIs) are devastating infections caused by either a single pathogen, predominantly Streptococcus pyogenes, or by multiple bacterial species. A better understanding of the pathogenic mechanisms underlying these different NSTI types could facilitate faster diagnostic and more effective therapeutic strategies. Here, we integrate microbial community profiling with host and pathogen(s) transcriptional analysis in patient biopsies to dissect the pathophysiology of streptococcal and polymicrobial NSTIs. We observe that the pathogenicity of polymicrobial communities is mediated by synergistic interactions between community members, fueling a cycle of bacterial colonization and inflammatory tissue destruction. In S. pyogenes NSTIs, expression of specialized virulence factors underlies infection pathophysiology. Furthermore, we identify a strong interferon-related response specific to S. pyogenes NSTIs that could be exploited as a potential diagnostic biomarker. Our study provides insights into the pathophysiology of mono- and polymicrobial NSTIs and highlights the potential of host-derived signatures for microbial diagnosis of NSTIs.

Date: 2019
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DOI: 10.1038/s41467-019-11722-8

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