CSF Levels of Elongation Factor Tu Is Associated With Increased Mortality in Malawian Adults With

Elongation factor Tu (EF-Tu) HIV—human immunodeficiency virus Streptococcus pneumoniae cerebrospinal fluid meningitis mortality proteomics

Journal

Frontiers in cellular and infection microbiology
ISSN: 2235-2988
Titre abrégé: Front Cell Infect Microbiol
Pays: Switzerland
ID NLM: 101585359

Informations de publication

Date de publication:
2020
Historique:
received: 07 09 2020
accepted: 10 11 2020
entrez: 28 12 2020
pubmed: 29 12 2020
medline: 22 6 2021
Statut: epublish

Résumé

Mortality from bacterial meningitis, predominately caused by CSF proteomes were analyzed by quantitative Mass-Spectrometry. Spectra were identified using the Swissprot human and TIGR4 pneumococcal protein libraries. Proteins were quantitated and analyzed against mortality. Unique proteins in PM were identified against published normal CSF proteome. Random-Forest models were used to test for protein signatures discriminating outcome. Proteins of interest were tested for their effects on growth and neutrophil opsonophagocytic killing of CSF proteomes were available for 57 Adults with PM (median age 32 years, 60% male, 70% HIV-1 co-infected, mortality 63%). Three hundred sixty individual human and 23 pneumococcal proteins were identified. Of the human protein hits, 30% were not expressed in normal CSF, and these were strongly associated with inflammation and primarily related to neutrophil activity. No human protein signature predicted outcome. However, expression of the essential Excessive

Sections du résumé

Background
Mortality from bacterial meningitis, predominately caused by
Materials/Methods
CSF proteomes were analyzed by quantitative Mass-Spectrometry. Spectra were identified using the Swissprot human and TIGR4 pneumococcal protein libraries. Proteins were quantitated and analyzed against mortality. Unique proteins in PM were identified against published normal CSF proteome. Random-Forest models were used to test for protein signatures discriminating outcome. Proteins of interest were tested for their effects on growth and neutrophil opsonophagocytic killing of
Results
CSF proteomes were available for 57 Adults with PM (median age 32 years, 60% male, 70% HIV-1 co-infected, mortality 63%). Three hundred sixty individual human and 23 pneumococcal proteins were identified. Of the human protein hits, 30% were not expressed in normal CSF, and these were strongly associated with inflammation and primarily related to neutrophil activity. No human protein signature predicted outcome. However, expression of the essential
Conclusions
Excessive

Identifiants

pubmed: 33363056
doi: 10.3389/fcimb.2020.603623
pmc: PMC7759504
doi:

Substances chimiques

Peptide Elongation Factor Tu EC 3.6.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

603623

Subventions

Organisme : Medical Research Council
ID : MR/K012053/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T016329/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 089671/B/09/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 101113/Z/13/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R00/1871/1
Pays : United Kingdom

Informations de copyright

Copyright © 2020 Wall, Brownridge, Laing, Terra, Mlozowa, Denis, Nyirenda, Allain, Ramos-Sevillano, Carrol, Collins, Gordon, Lalloo, Wren, Beynon, Heyderman and Brown.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Emma C Wall (EC)

The Francis Crick Institute, London, United Kingdom.
Division of Infection and Immunity, University College London, London, United Kingdom.
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.

Philip Brownridge (P)

Centre for Proteomics, Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Gavin Laing (G)

Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Vanessa S Terra (VS)

London School of Hygiene and Tropical Medicine, London, United Kingdom.

Veronica Mlozowa (V)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.

Brigitte Denis (B)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.

Mulinda Nyirenda (M)

Adult Emergency Trauma Centre, Queen Elizabeth Central Hospital, Ministry of Health, Blantyre, Malawi.
College of Medicine, University of Malawi, Blantyre, Malawi.

Theresa Allain (T)

College of Medicine, University of Malawi, Blantyre, Malawi.

Elisa Ramos-Sevillano (E)

UCL Respiratory, Division of Medicine, University College London, London, United Kingdom.

Enitan Carrol (E)

Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.

Andrea Collins (A)

Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Liverpool University Hospital Foundation Trust, Liverpool, United Kingdom.

Stephen B Gordon (SB)

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.
Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

David G Lalloo (DG)

Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Brendan Wren (B)

London School of Hygiene and Tropical Medicine, London, United Kingdom.

Robert Beynon (R)

Centre for Proteomics, Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

Robert S Heyderman (RS)

Division of Infection and Immunity, University College London, London, United Kingdom.
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.

Jeremy S Brown (JS)

UCL Respiratory, Division of Medicine, University College London, London, United Kingdom.

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