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Dual RNASeq reveals NTHi-macrophage transcriptomic changes during intracellular persistence

ABSTRACT: Dual RNASeq reveals NTHi-macrophage transcriptomic changes during intracellular persistence

PROVIDER: PRJNA746945 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15147300_1.fastq.gz	Fastqsanger.gz
	SRR15147300_2.fastq.gz	Fastqsanger.gz
	SRR15147301_1.fastq.gz	Fastqsanger.gz
	SRR15147301_2.fastq.gz	Fastqsanger.gz
	SRR15147302_1.fastq.gz	Fastqsanger.gz

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Dual RNASeq reveals NTHi-macrophage transcriptomic changes during intracellular persistence

Project description:Nontypeable Haemophilus influenzae (NTHi) is a pathobiont which chronically colonises the airway of individuals with chronic respiratory disease. It is unclear how NTHi persists in the airway, however accumulating evidence suggests that NTHi can invade and persist within macrophages. To better understand the mechanisms of NTHi persistence within macrophages, this work developed an in vitro model of NTHi intracellular persistence using human monocyte-derived macrophages (MDM). Dual RNA Sequencing was used to assess MDM and NTHi transcriptomic regulation occurring simultaneously during NTHi persistence. This work demonstrates that NTHi can invade and persist within human macrophages. Macrophages activate innate immune responses, whereas NTHi persistence was facilitated by transcriptomic adaptations in bacterial metabolic, stress response and ribosome pathways. This research provides transcriptomic insights into NTHi-macrophage interactions, enhances our understanding of how NTHi can utilise host immune cells to chronically colonise the airway and identifies potential bacterial gene pathways that may be attractive therapeutic targets

2021-08-23 | GSE180166 | GEO

Dual RNASeq Reveals NTHi-Macrophage Transcriptomic Changes During Intracellular Persistence.

Project description:Nontypeable Haemophilus influenzae (NTHi) is a pathobiont which chronically colonises the airway of individuals with chronic respiratory disease and is associated with poor clinical outcomes. It is unclear how NTHi persists in the airway, however accumulating evidence suggests that NTHi can invade and persist within macrophages. To better understand the mechanisms of NTHi persistence within macrophages, we developed an in vitro model of NTHi intracellular persistence using human monocyte-derived macrophages (MDM). Dual RNA Sequencing was used to assess MDM and NTHi transcriptomic regulation occurring simultaneously during NTHi persistence. Analysis of the macrophage response to NTHi identified temporally regulated transcriptomic profiles, with a specific 'core' profile displaying conserved expression of genes across time points. Gene list enrichment analysis identified enrichment of immune responses in the core gene set, with KEGG pathway analysis revealing specific enrichment of intracellular immune response pathways. NTHi persistence was facilitated by modulation of bacterial metabolic, stress response and ribosome pathways. Levels of NTHi genes bioC, mepM and dps were differentially expressed by intracellular NTHi compared to planktonic NTHi, indicating that the transcriptomic adaption was distinct between the two different NTHi lifestyles. Overall, this study provides crucial insights into the transcriptomic adaptations facilitating NTHi persistence within macrophages. Targeting these reported pathways with novel therapeutics to reduce NTHi burden in the airway could be an effective treatment strategy given the current antimicrobial resistance crisis and lack of NTHi vaccines.

| S-EPMC8419319 | biostudies-literature

Transcriptome analysis of NTHi 86-028NPrpsL, NTHi 86-028NPrpsL∆fur, NTHi 86-028NPrpsL∆fur∆hrrF, NTHi 86-028NPrpsL∆fur∆hrrF3' strains

2014-08-26 | GSE58891 | GEO

Transcriptome analysis of NTHi 86-028NPrpsL, NTHi 86-028NPrpsLM-bM-^HM-^Ffur, NTHi 86-028NPrpsLM-bM-^HM-^FfurM-bM-^HM-^FhrrF, NTHi 86-028NPrpsLM-bM-^HM-^FfurM-bM-^HM-^FhrrF3' strains

Project description: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. Previous work has identified a small RNA, HrrF, that is Fur-regulated in NTHi 86-028NPrpsL.To understand the contribution made by HrrF to gene regulation in NTHi, hrrF was deleted in the NTHi strain 86-028NPrpsLM-bM-^HM-^Ffur. Using RNA-Seq, we identified protein-encoding genes whose expression was repressed or activated by HrrF. These data comprise transcriptional anaylses of an rpsL mutant of 86-028NP, an isogenic fur mutant of 86-028NPrpsL, an isogenic fur mutant of 86-028NPrpsL also containing a full deletion of hrrF, and an isogenic fur mutant of 86-028NPrpsL also containing a deletion of only the 3' portion of hrrF. All strains were grown in defined medium containing 10 M-BM-5g/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 four strains of nontypeable Haemophilus influenzae which include NTHi 86-028NPrpsL, NTHi 86-028NPrpsLM-bM-^HM-^Ffur, NTHi 86-028NPrpsLM-bM-^HM-^FfurM-bM-^HM-^FhrrF, and NTHi 86-028NPrpsLM-bM-^HM-^FfurM-bM-^HM-^FhrrF3' strains. For each strain three biological replicates were analyzed.

2014-08-26 | E-GEOD-58891 | biostudies-arrayexpress

RNA SEQ NTHi modA10

Project description:Comparison of RNA expression profiles from NTHi strain R2866 expressing methyltransferase ModA10 (ON) or not (LOCK_OFF).

2019-04-15 | GSE129786 | GEO

RNA SEQ NTHi modA2

Project description:Comparison of RNA expression profiles from NTHi strain 723 strains expressing methyltransferase ModA2 (ON) or not (OFF)

2020-10-25 | GSE106187 | GEO

RNA SEQ NTHi modA18

Project description:Comparison of RNA expression profiles from NTHi strain 84P36H1 strains expressing methyltransferase ModA18 (ON) or not (OFF).

2019-04-13 | GSE129764 | GEO

RNA SEQ NTHi modA15

Project description:Comparison of RNA expression profiles from NTHi strain 10P129H1 strains expressing methyltransferase ModA15 (ON) or not (OFF).

2019-04-13 | GSE129761 | GEO

Sustained Reprioritization of metabolic pathways is associated with persistence and biofilm formation in non-typeable Haemophilus influenzae

Project description:Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that has an essential requirement for heme-iron acquisition and must overcome host nutritional immunity to survive and persist in the host. In this study we examine the metabolic contributions to persistence using the evolved NTHI strain, RM33. Quantitative analyses identified 29 proteins, 55 transcripts and 31 metabolites that significantly changed within in vitro biofilms formed by RM33.

2019-08-02 | MSV000084166 | MassIVE

RNA SEQ NTHi modA18

Project description:RNA SEQ NTHi modA18

| PRJNA532651 | ENA