Email updates

Keep up to date with the latest news and content from BMC Infectious Diseases and BioMed Central.

Open Access Highly Accessed Research article

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

Sok Kean Khoo1, David Petillo2, Mrutyunjaya Parida1, Aik Choon Tan3, James H Resau4 and Stephen K Obaro5*

Author Affiliations

1 Laboratory of Microarray Technology, Van Andel Research Institute, Grand Rapids, MI, USA

2 Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI, USA

3 Department of Medicine, University of Colorado Denver, Aurora, CO, USA

4 Laboratory of Analytical, Cellular, and Molecular Microscopy, Van Andel Research Institute, Grand Rapids, MI, USA

5 Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI, USA

For all author emails, please log on.

BMC Infectious Diseases 2011, 11:241  doi:10.1186/1471-2334-11-241

Published: 13 September 2011

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.