A Iwasaki

Aik Choon Tan

AW Ravna

B Vanhollebeke

CM Parry

David Petillo

DR Flower

E Mweu

FJ Cooke

H Andersson

HR Conti

HS Kim

IA Goncharova

J Wijnholds

JA Whitaker

James H Resau

K Hoebe

KJ Livak

KP Klugman

L Franchi

LJ Thompson

M Keuter

M Raffatellu

MA Bachman

MA Fischbach

MI Ardura

MJ Griffiths

Mrutyunjaya Parida

R Thomson

RM Tsolis

RP Wilson

S Dutta

S Obaro

SJ Aujla

Sok Kean Khoo

Stephen K Obaro

T Oguri

TH Flo

W Huang da

ZA Bhutta

BMC Infectious Diseases

English

PubMed

Springer - Publisher Connector

Host response transcriptional profiling reveals extracellular components and ABC (ATP-binding cassette) transporters gene enrichment in typhoid fever-infected Nigerian children

Abstract
          
            Background
            
              Salmonella enterica serovar Typhi (S. Typhi) is a human-specific pathogen that causes typhoid fever, and remains a global health problem especially in developing countries. Its pathogenesis is complex and host response is poorly understood. In Africa, typhoid fever can be a major cause of morbidity in young infected children. The onset of the illness is insidious and clinical diagnosis is often unreliable. Gold standard blood culture diagnostic services are limited, thus rapid, sensitive, and affordable diagnostic test is essential in poor-resourced clinical settings. Routine typhoid fever vaccination is highly recommended but currently licensed vaccines provide only 55-75% protection. Recent epidemiological studies also show the rapid emergence of multi-drug resistant S. Typhi strains. High-throughput molecular technologies, such as microarrays, can dissect the molecular mechanisms of host responses which are S. Typhi-specific to provide a comprehensive genomic component of immunological responses and suggest new insights for diagnosis and treatment.
          
          
            Methods
            Global transcriptional profiles of S. Typhi-infected young Nigerian children were obtained from their peripheral blood and compared with that of other bacteremic infections using Agilent gene expression microarrays. The host-response profiles of the same patients in acute vs. convalescent phases were also determined. The top 96-100 differentially-expressed genes were identified and four genes were validated by quantitative real-time PCR. Gene clusters were obtained and functional pathways were predicted by DAVID (Database for Annotation, Visualization and Integrated Discovery).
          
          
            Results
            Transcriptional profiles from S. Typhi-infected children could be distinguished from those of other bacteremic infections. Enriched gene clusters included genes associated with extracellular peptides/components such as lipocalin (LCN2) and systemic immune response which is atypical in bacterial invasion. Distinct gene expression profiles can also be obtained from acute vs. convalescent phase during typhoid fever infection. We found novel down-regulation of ABC (ATP-binding cassette) transporters genes such as ABCA7, ABCC5, and ABCD4 and ATPase activity as the highest enriched pathway.
          
          
            Conclusions
            We identified unique extracellular components and ABC transporters gene enrichments in typhoid fever-infected Nigerian children, which have never been reported. These enriched gene clusters may represent novel targeted pathways to improve diagnostic, prognostic, therapeutic and next-generation vaccine strategies for typhoid fever in Africa.
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Gene expression patterns of dengue virus-infected children from nicaragua reveal a distinct signature of increased metabolism.

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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3189140

Host response transcriptional profiling reveals extracellular components and ABC (ATP-binding cassette) transporters gene enrichment in typhoid fever-infected Nigerian children

Abstract

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