Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/87132
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Type: Journal article
Title: A functional genomics catalogue of activated transcription factors during pathogenesis of pneumococcal disease
Author: Mahdi, L.
Deihimi, T.
Zamansani, F.
Fruzangohar, M.
Adelson, D.
Paton, J.
Ogunniyi, A.
Ebrahimie, E.
Citation: BMC Genomics, 2014; 15(1):769-1-769-15
Publisher: BioMed Central
Issue Date: 2014
ISSN: 1471-2164
1471-2164
Statement of
Responsibility: 
Layla K Mahdi, Tahereh Deihimi, Fatemeh Zamansani, Mario Fruzangohar, David L Adelson, James C Paton, Abiodun D Ogunniyi, and Esmaeil Ebrahimie
Abstract: BACKGROUND: Streptococcus pneumoniae (the pneumococcus) is the world's foremost microbial pathogen, killing more people each year than HIV, TB or malaria. The capacity to penetrate deeper host tissues contributes substantially to the ability of this organism to cause disease. Here we investigated, for the first time, functional genomics modulation of 3 pneumococcal strains (serotype 2 [D39], serotype 4 [WCH43] and serotype 6A [WCH16]) during transition from the nasopharynx to lungs to blood and to brain of mice at both promoter and domain activation levels. RESULTS: We found 7 highly activated transcription factors (TFs) [argR, codY, hup, rpoD, rr02, scrR and smrC] capable of binding to a large number of up-regulated genes, potentially constituting the regulatory backbone of pneumococcal pathogenesis. Strain D39 showed a distinct profile in employing a large number of TFs during blood infection. Interestingly, the same highly activated TFs used by D39 in blood are also used by WCH16 and WCH43 during brain infection. This indicates that different pneumococcal strains might activate a similar set of TFs and regulatory elements depending on the final site of infection. Hierarchical clustering analysis showed that all the highly activated TFs, except rpoD, clustered together with a high level of similarity in all 3 strains, which might suggest redundancy in the regulatory roles of these TFs during infection. Discriminant function analysis of the TFs in various niches highlights differential regulatory backgrounds of the 3 strains, and pathogenesis data confirms codY as the most significant predictor discriminating between these strains in various niches, particularly in the blood. Moreover, the predicted TF and domain activation profiles of the 3 strains correspond with their distinct pathogenicity characteristics. CONCLUSIONS: Our findings suggest that the pneumococcus changes the short binding sites in the promoter regions of genes in a niche-specific manner to enhance its ability to disseminate from one host niche to another. This study provides a framework for an improved understanding of the dynamics of pneumococcal pathogenesis, and opens a new avenue into similar investigations in other pathogenic bacteria.
Keywords: Animals; Mice; Streptococcus pneumoniae; Pneumococcal Infections; Bacterial Proteins; Transcription Factors; Cluster Analysis; Proteomics; Genomics; Gene Expression Regulation, Bacterial; Binding Sites; Protein Binding; Female; Gene Regulatory Networks; Protein Interaction Domains and Motifs; Promoter Regions, Genetic; Genetic Fitness
Rights: © 2014 Mahdi et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
RMID: 0030008990
DOI: 10.1186/1471-2164-15-769
Grant ID: http://purl.org/au-research/grants/nhmrc/627142
http://purl.org/au-research/grants/nhmrc/565526
Appears in Collections:Molecular and Biomedical Science publications

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