Proteomics

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Identification of protein biomarkers for pneumococcal meningitis in children C4PR_LIV

ABSTRACT: Bacterial meningitis is usually fatal without treatment. Prompt and accurate diagnosis coupled with the timely administration of parenteral antibiotics is necessary in order to save lives. We used label-free mass spectrometry based quantitative proteomics to identify specific protein signatures in cerebrospinal fluid from Malawian children with Streptococcus pneumoniae infection, the leading cause of bacterial meningitis in children, elderly and people infected with Human Immunodeficiency Virus. Samples were analysed in two independent cohorts (cases and controls, n=12 for the discovery cohort and n=16 for the verification cohort). The protein profiles clearly discriminated cases and controls. Proteins involved in the immune response and exosome cell signaling were significantly enriched in the infected samples. Several S. pneumoniae membrane proteins were identified suggesting these as potential therapeutic targets. For both cohorts, over 200 human proteins were up and down-regulated in children with confirmed S. pneumoniae infection in comparison with controls. Compiling proteins up- and down- regulated in both discovery and verification cohorts, we generated a comprehensive list of over 140 proteins from which diagnostic biomarkers could be nominated. For a panel of five selected proteins (cathelicidin, ceruloplasmin, myeloperoxidase, cystatin C and protein S100A8/S100 A9), we additionally verified the label-free results by automated quantitative western blot immunoassays (Simple Western™), with excellent agreement between the two experimental approaches. The proteins identified in our study could form the basis of development of a biomarker panel for rapid diagnosis. Our results could lead to the development of point-of-care assays to inform diagnosis, and to nominate new targets for drugs and vaccines to improve disease management and consequently to enhance the prognosis of children with bacterial meningitis.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Streptococcal Meningitis

SUBMITTER: Guadalupe Gomez Baena  

LAB HEAD: Prof. Rob J. Beynon

PROVIDER: PXD004219 | Pride | 2017-08-03

REPOSITORIES: Pride

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Publications

Quantitative Proteomics of Cerebrospinal Fluid in Paediatric Pneumococcal Meningitis.

Gómez-Baena Guadalupe G   Bennett Richard J RJ   Martínez-Rodríguez Carmen C   Wnęk Małgorzata M   Laing Gavin G   Hickey Graeme G   McLean Lynn L   Beynon Robert J RJ   Carrol Enitan D ED  

Scientific reports 20170801 1

Streptococcus pneumoniae is responsible for diseases causing major global public health problems, including meningitis, pneumonia and septicaemia. Despite recent advances in antimicrobial therapy, pneumococcal meningitis remains a life-threatening disease. Furthermore, long-term sequelae are a major concern for survivors. Hence, a better understanding of the processes occurring in the central nervous system is crucial to the development of more effective management strategies. We used mass spect  ...[more]