Project description:Transcriptome analysis of NTHi 86-028NPrpsL, NTHi 86-028NPrpsL∆fur, and NTHi 86-028NPrpsL∆fur(pT-fur) strains Nontypeable Haemophilus influenzae (NTHi) is a commensal microorganism of the normal human nasopharyngeal flora, yet also an opportunistic pathogen of the upper and lower respiratory tracts. Changes in gene expression patterns in response to host microenvironments are likely critical for survival. One such system of gene regulation is the ability to carefully regulate iron uptake. A central regulatory system that controls iron uptake, mediated by the ferric uptake regulator Fur, is present in multiple bacteria, including NTHi. To understand the regulation of iron homeostasis in NTHi, fur was deleted in the NTHi strain 86-028NPrpsL. Using RNA-Seq, we identified both protein-encoding and small RNA genes whose expression was repressed or activated by Fur. Overall design: These data comprise transcriptional anaylses of an rpsL mutant of 86-028NP, an isogenic fur mutant of 86-028NPrpsL and a complemented fur mutant strain. All strains were grown in defined medium containing 10 µg/ml human hemoglobin to mid-log phase. Cells were then harvested and RNA extracted. A total of three biological replicates were generated for these analyses. Analysis of transcriptomes using the Illumina HiSeq 2000 of three strains of nontypeable Haemophilus influenzae which include NTHi 86-028NPrpsL, NTHi 86-028NPrpsL∆fur, and NTHi 86-028NPrpsL∆fur(pT-fur) strains. For each strain three biological replicates were analyzed
Project description:Background: Haemophilus influenzae has an absolute aerobic growth requirement for heme and has developed multiple complex mechanisms to obtain this essential nutrient. Although an understanding of the heme acquisition mechanisms of H. influenzae is emerging, significant gaps remain to be elucidated. In a previous study 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 initial observations by determining the iron/heme regulons of two additional H. influenzae clinical isolates, i.e. the type b isolate 10810 and the nontypeable isolate R2866, to characterize the core iron/heme regulon of the species. Results: A microarray chip was designed to incorporate probes for all of the genes of H. influenzae isolates 10810 and R2866, and microarray studies were performed to compare gene expression under iron/heme-replete and iron/heme-restricted conditions for each isolate. Of 1820 ORFs on the array corresponding to R2866 genes, 363 were significantly differentially expressed. Of these 363 genes, 233 were maximally transcribed under iron/heme-replete conditions and 130 were preferentially transcribed in iron/heme-restricted conditions. Of the 1883 ORFs representing genes of strain10810, 351 were significantly differentially transcribed, 150 of these were preferentially transcribed in iron/heme-replete conditions and 201 were preferentially transcribed in iron/heme-restricted conditions. Comparison of the data sets indicated that 163 genes were similarly regulated in both isolates and that 74 of these also exhibited similar patterns of regulation in strain Rd KW20. Conclusion: This study provides evidence for a core of H. influenzae genes that are regulated by the availability of iron and/or heme in the growth environment. Elucidation of this core regulon provides targets for investigation of genes with an unrecognized role in iron and heme homeostasis, as well as other potential virulence determinants. In addition, the set of core genes potentially provides targets for therapeutic and vaccine designs since these products of these genes are likely to be preferentially expressed during growth in iron/heme restricted sites of the human body. This SuperSeries is composed of the following subset Series: GSE11349: Transcriptional profiling of FeHm effects on Haemophilus influenzae R2866 GSE11354: Transcriptional profiling of FeHm effects on Haemophilus influenzae 10810 Keywords: SuperSeries Refer to individual Series
Project description:Schilling2000- Genome-scale metabolic network
of Haemophilus influenzae (iCS400)
This model is described in the article:
Assessment of the metabolic
capabilities of Haemophilus influenzae Rd through a
genome-scale pathway analysis.
Schilling CH, Palsson BO.
J. Theor. Biol. 2000 Apr; 203(3):
The annotated full DNA sequence is becoming available for a
growing number of organisms. This information along with
additional biochemical and strain-specific data can be used to
define metabolic genotypes and reconstruct cellular metabolic
networks. The first free-living organism for which the entire
genomic sequence was established was Haemophilus influenzae.
Its metabolic network is reconstructed herein and contains 461
reactions operating on 367 intracellular and 84 extracellular
metabolites. With the metabolic reaction network established,
it becomes necessary to determine its underlying pathway
structure as defined by the set of extreme pathways. The H.
influenzae metabolic network was subdivided into six subsystems
and the extreme pathways determined for each subsystem based on
stoichiometric, thermodynamic, and systems-specific
constraints. Positive linear combinations of these pathways can
be taken to determine the extreme pathways for the complete
system. Since these pathways span the capabilities of the full
system, they could be used to address a number of important
physiological questions. First, they were used to reconcile and
curate the sequence annotation by identifying reactions whose
function was not supported in any of the extreme pathways.
Second, they were used to predict gene products that should be
co-regulated and perhaps co-expressed. Third, they were used to
determine the composition of the minimal substrate requirements
needed to support the production of 51 required metabolic
products such as amino acids, nucleotides, phospholipids, etc.
Fourth, sets of critical gene deletions from core metabolism
were determined in the presence of the minimal substrate
conditions and in more complete conditions reflecting the
environmental niche of H. influenzae in the human host. In the
former case, 11 genes were determined to be critical while six
remained critical under the latter conditions. This study
represents an important milestone in theoretical biology,
namely the establishment of the first extreme pathway structure
of a whole genome.
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