Molecular profiling of tissue biopsies reveals unique signatures associated with streptococcal necrotizing soft tissue infections
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Molecular profiling of tissue biopsies reveals unique signatures associated with streptococcal necrotizing soft tissue infections. / Thänert, Robert; Itzek, Andreas; Hoßmann, Jörn; Hamisch, Domenica; Madsen, Martin Bruun; Hyldegaard, Ole; Skrede, Steinar; Bruun, Trond; Norrby-Teglund, Anna; INFECT Study Group; Medina, Eva; Pieper, Dietmar H.
In: Nature Communications, Vol. 10, 3846, 08.2019.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Molecular profiling of tissue biopsies reveals unique signatures associated with streptococcal necrotizing soft tissue infections
AU - Thänert, Robert
AU - Itzek, Andreas
AU - Hoßmann, Jörn
AU - Hamisch, Domenica
AU - Madsen, Martin Bruun
AU - Hyldegaard, Ole
AU - Skrede, Steinar
AU - Bruun, Trond
AU - Norrby-Teglund, Anna
AU - INFECT Study Group
AU - Medina, Eva
AU - Pieper, Dietmar H.
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-019-11722-8
DO - 10.1038/s41467-019-11722-8
M3 - Journal article
C2 - 31451691
AN - SCOPUS:85071480626
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 3846
ER -
ID: 240244462