Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Integrated univariate, multivariate and correlation-based network analyses reveal metabolite-specific effects on bacterial growth and biofilm formation in necrotizing soft tissue infections

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{85e998d26bc24676860f5ec63a22b4b6,
title = "Integrated univariate, multivariate and correlation-based network analyses reveal metabolite-specific effects on bacterial growth and biofilm formation in necrotizing soft tissue infections",
abstract = "Necrotizing soft-tissue infections (NSTIs) have multiple causes, risk factors, anatomical locations, and pathogenic mechanisms. In patients with NSTI, circulating metabolites may serve as a substrate having impact on bacterial adaptation at the site of infection. Metabolic signatures associated with NSTI may reveal the potential to be useful as diagnostic and prognostic markers and novel targets for therapy. This study used untargeted metabolomics analyses of plasma from NSTI patients (n = 34) and healthy (noninfected) controls (n = 24) to identify the metabolic signatures and connectivity patterns among metabolites associated with NSTI. Metabolite-metabolite association networks were employed to compare the metabolic profiles of NSTI patients and noninfected surgical controls. Out of 97 metabolites detected, the abundance of 33 was significantly altered in NSTI patients. Analysis of metabolite-metabolite association networks showed a more densely connected network: Specifically, 20 metabolites differentially connected between NSTI and controls. A selected set of significantly altered metabolites was tested in vitro to investigate potential influence on NSTI group A streptococcal strain growth and biofilm formation. Using chemically defined media supplemented with the selected metabolites, ornithine, ribose, urea, and glucuronic acid, revealed metabolite-specific effects on both bacterial growth and biofilm formation. This study identifies for the first time an NSTI-specific metabolic signature with implications for optimized diagnostics and therapies.",
keywords = "bacterial infection, differential network analysis, metabolomics, necrotizing fasciitis, necrotizing soft-tissue infections, streptococcus",
author = "Muhammad Afzal and Edoardo Saccenti and Martin Madsen and Hansen, {Marco Bo} and Ole Hyldegaard and Steinar Skrede and {Martins Dos Santos}, Vitor and {Norrby Teglund}, Anna and Mattias Svensson",
year = "2020",
month = "2",
day = "7",
doi = "10.1021/acs.jproteome.9b00565",
language = "English",
volume = "19",
pages = "688--698",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
number = "2",

}

RIS

TY - JOUR

T1 - Integrated univariate, multivariate and correlation-based network analyses reveal metabolite-specific effects on bacterial growth and biofilm formation in necrotizing soft tissue infections

AU - Afzal, Muhammad

AU - Saccenti, Edoardo

AU - Madsen, Martin

AU - Hansen, Marco Bo

AU - Hyldegaard, Ole

AU - Skrede, Steinar

AU - Martins Dos Santos, Vitor

AU - Norrby Teglund, Anna

AU - Svensson, Mattias

PY - 2020/2/7

Y1 - 2020/2/7

N2 - Necrotizing soft-tissue infections (NSTIs) have multiple causes, risk factors, anatomical locations, and pathogenic mechanisms. In patients with NSTI, circulating metabolites may serve as a substrate having impact on bacterial adaptation at the site of infection. Metabolic signatures associated with NSTI may reveal the potential to be useful as diagnostic and prognostic markers and novel targets for therapy. This study used untargeted metabolomics analyses of plasma from NSTI patients (n = 34) and healthy (noninfected) controls (n = 24) to identify the metabolic signatures and connectivity patterns among metabolites associated with NSTI. Metabolite-metabolite association networks were employed to compare the metabolic profiles of NSTI patients and noninfected surgical controls. Out of 97 metabolites detected, the abundance of 33 was significantly altered in NSTI patients. Analysis of metabolite-metabolite association networks showed a more densely connected network: Specifically, 20 metabolites differentially connected between NSTI and controls. A selected set of significantly altered metabolites was tested in vitro to investigate potential influence on NSTI group A streptococcal strain growth and biofilm formation. Using chemically defined media supplemented with the selected metabolites, ornithine, ribose, urea, and glucuronic acid, revealed metabolite-specific effects on both bacterial growth and biofilm formation. This study identifies for the first time an NSTI-specific metabolic signature with implications for optimized diagnostics and therapies.

AB - Necrotizing soft-tissue infections (NSTIs) have multiple causes, risk factors, anatomical locations, and pathogenic mechanisms. In patients with NSTI, circulating metabolites may serve as a substrate having impact on bacterial adaptation at the site of infection. Metabolic signatures associated with NSTI may reveal the potential to be useful as diagnostic and prognostic markers and novel targets for therapy. This study used untargeted metabolomics analyses of plasma from NSTI patients (n = 34) and healthy (noninfected) controls (n = 24) to identify the metabolic signatures and connectivity patterns among metabolites associated with NSTI. Metabolite-metabolite association networks were employed to compare the metabolic profiles of NSTI patients and noninfected surgical controls. Out of 97 metabolites detected, the abundance of 33 was significantly altered in NSTI patients. Analysis of metabolite-metabolite association networks showed a more densely connected network: Specifically, 20 metabolites differentially connected between NSTI and controls. A selected set of significantly altered metabolites was tested in vitro to investigate potential influence on NSTI group A streptococcal strain growth and biofilm formation. Using chemically defined media supplemented with the selected metabolites, ornithine, ribose, urea, and glucuronic acid, revealed metabolite-specific effects on both bacterial growth and biofilm formation. This study identifies for the first time an NSTI-specific metabolic signature with implications for optimized diagnostics and therapies.

KW - bacterial infection

KW - differential network analysis

KW - metabolomics

KW - necrotizing fasciitis

KW - necrotizing soft-tissue infections

KW - streptococcus

U2 - 10.1021/acs.jproteome.9b00565

DO - 10.1021/acs.jproteome.9b00565

M3 - Journal article

VL - 19

SP - 688

EP - 698

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 2

ER -

ID: 58863173