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Streptococcus pyogenes Transcriptome Changes in the Inflammatory Environment of Necrotizing Fasciitis

Streptococcus pyogenes is a major cause of necrotizing fasciitis, a life-threatening subcutaneous soft-tissue infection. At the host infection site, the local environment and interactions between the host and bacteria have effects on bacterial gene expression profiles, while the gene expression patt...

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Autores principales: Hirose, Yujiro, Yamaguchi, Masaya, Okuzaki, Daisuke, Motooka, Daisuke, Hamamoto, Hiroshi, Hanada, Tomoki, Sumitomo, Tomoko, Nakata, Masanobu, Kawabata, Shigetada
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803311/
https://www.ncbi.nlm.nih.gov/pubmed/31471300
http://dx.doi.org/10.1128/AEM.01428-19
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author Hirose, Yujiro
Yamaguchi, Masaya
Okuzaki, Daisuke
Motooka, Daisuke
Hamamoto, Hiroshi
Hanada, Tomoki
Sumitomo, Tomoko
Nakata, Masanobu
Kawabata, Shigetada
author_facet Hirose, Yujiro
Yamaguchi, Masaya
Okuzaki, Daisuke
Motooka, Daisuke
Hamamoto, Hiroshi
Hanada, Tomoki
Sumitomo, Tomoko
Nakata, Masanobu
Kawabata, Shigetada
author_sort Hirose, Yujiro
collection PubMed
description Streptococcus pyogenes is a major cause of necrotizing fasciitis, a life-threatening subcutaneous soft-tissue infection. At the host infection site, the local environment and interactions between the host and bacteria have effects on bacterial gene expression profiles, while the gene expression pattern of S. pyogenes related to this disease remains unknown. In this study, we used a mouse model of necrotizing fasciitis and performed RNA-sequencing (RNA-seq) analysis of S. pyogenes M1T1 strain 5448 by isolating total RNA from infected hind limbs obtained at 24, 48, and 96 h postinfection. RNA-seq analysis results identified 483 bacterial genes whose expression was consistently altered in the infected hindlimbs compared to their expression under in vitro conditions. Genes showing consistent enrichment during infection included 306 encoding molecules involved in virulence, carbohydrate utilization, amino acid metabolism, trace-metal transport, and the vacuolar ATPase transport system. Surprisingly, drastic upregulation of 3 genes, encoding streptolysin S precursor (sagA), cysteine protease (speB), and secreted DNase (spd), was noted in the present mouse model (log(2) fold change, >6.0, >9.4, and >7.1, respectively). Conversely, the number of consistently downregulated genes was 177, including those associated with the oxidative stress response and cell division. These results suggest that in necrotizing fasciitis, S. pyogenes shows an altered metabolism, decreased cell proliferation, and upregulation of expression of major toxins. Our findings are considered to provide critical information for developing novel treatment strategies and vaccines for necrotizing fasciitis. IMPORTANCE Necrotizing fasciitis, a life-threatening subcutaneous soft-tissue infection, is principally caused by S. pyogenes. The inflammatory environment at the site of infection causes global gene expression changes for survival of the bacterium and pathogenesis. However, no known study regarding transcriptomic profiling of S. pyogenes in cases of necrotizing fasciitis has been presented. We identified 483 bacterial genes whose expression was consistently altered during infection. Our results showed that S. pyogenes infection induces drastic upregulation of the expression of virulence-associated genes and shifts metabolic pathway usage. In particular, high-level expression of toxins, such as cytolysins, proteases, and nucleases, was observed at infection sites. In addition, genes identified as consistently enriched included those related to metabolism of arginine and histidine as well as carbohydrate uptake and utilization. Conversely, genes associated with the oxidative stress response and cell division were consistently downregulated during infection. The present findings provide useful information for establishing novel treatment strategies.
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spelling pubmed-68033112019-10-28 Streptococcus pyogenes Transcriptome Changes in the Inflammatory Environment of Necrotizing Fasciitis Hirose, Yujiro Yamaguchi, Masaya Okuzaki, Daisuke Motooka, Daisuke Hamamoto, Hiroshi Hanada, Tomoki Sumitomo, Tomoko Nakata, Masanobu Kawabata, Shigetada Appl Environ Microbiol Environmental Microbiology Streptococcus pyogenes is a major cause of necrotizing fasciitis, a life-threatening subcutaneous soft-tissue infection. At the host infection site, the local environment and interactions between the host and bacteria have effects on bacterial gene expression profiles, while the gene expression pattern of S. pyogenes related to this disease remains unknown. In this study, we used a mouse model of necrotizing fasciitis and performed RNA-sequencing (RNA-seq) analysis of S. pyogenes M1T1 strain 5448 by isolating total RNA from infected hind limbs obtained at 24, 48, and 96 h postinfection. RNA-seq analysis results identified 483 bacterial genes whose expression was consistently altered in the infected hindlimbs compared to their expression under in vitro conditions. Genes showing consistent enrichment during infection included 306 encoding molecules involved in virulence, carbohydrate utilization, amino acid metabolism, trace-metal transport, and the vacuolar ATPase transport system. Surprisingly, drastic upregulation of 3 genes, encoding streptolysin S precursor (sagA), cysteine protease (speB), and secreted DNase (spd), was noted in the present mouse model (log(2) fold change, >6.0, >9.4, and >7.1, respectively). Conversely, the number of consistently downregulated genes was 177, including those associated with the oxidative stress response and cell division. These results suggest that in necrotizing fasciitis, S. pyogenes shows an altered metabolism, decreased cell proliferation, and upregulation of expression of major toxins. Our findings are considered to provide critical information for developing novel treatment strategies and vaccines for necrotizing fasciitis. IMPORTANCE Necrotizing fasciitis, a life-threatening subcutaneous soft-tissue infection, is principally caused by S. pyogenes. The inflammatory environment at the site of infection causes global gene expression changes for survival of the bacterium and pathogenesis. However, no known study regarding transcriptomic profiling of S. pyogenes in cases of necrotizing fasciitis has been presented. We identified 483 bacterial genes whose expression was consistently altered during infection. Our results showed that S. pyogenes infection induces drastic upregulation of the expression of virulence-associated genes and shifts metabolic pathway usage. In particular, high-level expression of toxins, such as cytolysins, proteases, and nucleases, was observed at infection sites. In addition, genes identified as consistently enriched included those related to metabolism of arginine and histidine as well as carbohydrate uptake and utilization. Conversely, genes associated with the oxidative stress response and cell division were consistently downregulated during infection. The present findings provide useful information for establishing novel treatment strategies. American Society for Microbiology 2019-10-16 /pmc/articles/PMC6803311/ /pubmed/31471300 http://dx.doi.org/10.1128/AEM.01428-19 Text en Copyright © 2019 Hirose et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Environmental Microbiology
Hirose, Yujiro
Yamaguchi, Masaya
Okuzaki, Daisuke
Motooka, Daisuke
Hamamoto, Hiroshi
Hanada, Tomoki
Sumitomo, Tomoko
Nakata, Masanobu
Kawabata, Shigetada
Streptococcus pyogenes Transcriptome Changes in the Inflammatory Environment of Necrotizing Fasciitis
title Streptococcus pyogenes Transcriptome Changes in the Inflammatory Environment of Necrotizing Fasciitis
title_full Streptococcus pyogenes Transcriptome Changes in the Inflammatory Environment of Necrotizing Fasciitis
title_fullStr Streptococcus pyogenes Transcriptome Changes in the Inflammatory Environment of Necrotizing Fasciitis
title_full_unstemmed Streptococcus pyogenes Transcriptome Changes in the Inflammatory Environment of Necrotizing Fasciitis
title_short Streptococcus pyogenes Transcriptome Changes in the Inflammatory Environment of Necrotizing Fasciitis
title_sort streptococcus pyogenes transcriptome changes in the inflammatory environment of necrotizing fasciitis
topic Environmental Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803311/
https://www.ncbi.nlm.nih.gov/pubmed/31471300
http://dx.doi.org/10.1128/AEM.01428-19
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