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The iron/heme regulated genes of Haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon

BACKGROUND: Haemophilus influenzae requires heme for aerobic growth and possesses multiple mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps in our knowledge remain. Unresolved issues include the...

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Autores principales: Whitby, Paul W, Seale, Thomas W, VanWagoner, Timothy M, Morton, Daniel J, Stull, Terrence L
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627913/
https://www.ncbi.nlm.nih.gov/pubmed/19128474
http://dx.doi.org/10.1186/1471-2164-10-6
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author Whitby, Paul W
Seale, Thomas W
VanWagoner, Timothy M
Morton, Daniel J
Stull, Terrence L
author_facet Whitby, Paul W
Seale, Thomas W
VanWagoner, Timothy M
Morton, Daniel J
Stull, Terrence L
author_sort Whitby, Paul W
collection PubMed
description BACKGROUND: Haemophilus influenzae requires heme for aerobic growth and possesses multiple mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps in our knowledge remain. Unresolved issues include the identities of all genes exhibiting altered transcription in response to iron and heme availability, the fraction of such genes functioning in iron/heme acquisition, and the heterogeneity of this gene set among clinical isolates. Previously we utilized H. influenzae strain Rd KW20 to demonstrate the utility of transcriptional profiling in defining the genes exhibiting altered transcription in response to environmental iron and heme levels. The current study expands upon those observations by determining the iron/heme modulons of two clinical isolates, the type b isolate 10810 and the nontypeable isolate R2866. These data are used to begin to define the core iron/heme modulon of the species. RESULTS: Microarray studies were performed to compare gene expression on transition from iron/heme-restricted to iron/heme-replete conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed: 233 were maximally transcribed under iron/heme-replete conditions and 130 under iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain 10810, 353 were significantly differentially transcribed: 150 were preferentially transcribed under iron/heme-replete conditions and 203 under iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes exhibited similar regulation in both isolates and that 74 of these exhibited similar patterns of regulation in Rd KW20. These comprise the putative core iron/heme modulon. CONCLUSION: This study provides evidence for a conserved core of H. influenzae genes the transcription of which is altered by the availability of iron and/or heme in the growth environment. Elucidation of this modulon provides a means to identify genes with unrecognized roles in iron/heme acquisition or homeostasis, unanticipated responsiveness to environmental levels of the micronutrients or potential roles in virulence. Defining these core genes is also of potential importance in identifying targets for therapeutic and vaccine designs since products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body.
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spelling pubmed-26279132009-01-17 The iron/heme regulated genes of Haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon Whitby, Paul W Seale, Thomas W VanWagoner, Timothy M Morton, Daniel J Stull, Terrence L BMC Genomics Research Article BACKGROUND: Haemophilus influenzae requires heme for aerobic growth and possesses multiple mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps in our knowledge remain. Unresolved issues include the identities of all genes exhibiting altered transcription in response to iron and heme availability, the fraction of such genes functioning in iron/heme acquisition, and the heterogeneity of this gene set among clinical isolates. Previously we utilized H. influenzae strain Rd KW20 to demonstrate the utility of transcriptional profiling in defining the genes exhibiting altered transcription in response to environmental iron and heme levels. The current study expands upon those observations by determining the iron/heme modulons of two clinical isolates, the type b isolate 10810 and the nontypeable isolate R2866. These data are used to begin to define the core iron/heme modulon of the species. RESULTS: Microarray studies were performed to compare gene expression on transition from iron/heme-restricted to iron/heme-replete conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed: 233 were maximally transcribed under iron/heme-replete conditions and 130 under iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain 10810, 353 were significantly differentially transcribed: 150 were preferentially transcribed under iron/heme-replete conditions and 203 under iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes exhibited similar regulation in both isolates and that 74 of these exhibited similar patterns of regulation in Rd KW20. These comprise the putative core iron/heme modulon. CONCLUSION: This study provides evidence for a conserved core of H. influenzae genes the transcription of which is altered by the availability of iron and/or heme in the growth environment. Elucidation of this modulon provides a means to identify genes with unrecognized roles in iron/heme acquisition or homeostasis, unanticipated responsiveness to environmental levels of the micronutrients or potential roles in virulence. Defining these core genes is also of potential importance in identifying targets for therapeutic and vaccine designs since products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body. BioMed Central 2009-01-07 /pmc/articles/PMC2627913/ /pubmed/19128474 http://dx.doi.org/10.1186/1471-2164-10-6 Text en Copyright © 2009 Whitby et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Whitby, Paul W
Seale, Thomas W
VanWagoner, Timothy M
Morton, Daniel J
Stull, Terrence L
The iron/heme regulated genes of Haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon
title The iron/heme regulated genes of Haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon
title_full The iron/heme regulated genes of Haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon
title_fullStr The iron/heme regulated genes of Haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon
title_full_unstemmed The iron/heme regulated genes of Haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon
title_short The iron/heme regulated genes of Haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon
title_sort iron/heme regulated genes of haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627913/
https://www.ncbi.nlm.nih.gov/pubmed/19128474
http://dx.doi.org/10.1186/1471-2164-10-6
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