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

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-11722-8

2041-1723

Robert Thänert, Andreas Itzek, Jörn Hoßmann, Domenica Hamisch, Martin Bruun Madsen, Ole Hyldegaard, Steinar Skrede, Trond Bruun, Anna Norrby‐Teglund, Oddvar Oppegaard, Eivind Rath, Torbjørn Nedrebø, Per Arnell, Anders Rosén, Peter Polzik, Marco Bo Hansen, Mattias Svensson, Johanna Snäll, Ylva Karlsson, Michael Nekludov, Eva Medina, Dietmar H. Pieper,

Antimicrobial Resistance in Staphylococcus

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.