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Haemophilus ducreyi transcriptome during human infection

ABSTRACT: To better understand the molecular mechanisms underlying Haemophilus ducreyi infection in humans, here we determined the transcriptional profile of H. ducreyi in human lesions using RNA-Seq and compared it to that of in vitro growth. We were able to show that the in vivo transcriptome did not resemble that of in vitro growth. Compared to the inoculum, H. ducreyi harvested from pustules differentially expressed ~120 genes, of which 68 were upregulated. A large proportion of the upregulated genes encoded homologs of proteins involved in nutrient transport, alternative carbon pathways, growth arrest response, heat shock response, and DNA recombination. H. ducreyi upregulated few genes or operons (hgbA, flp-tad, and lspB-lspA2) required for human infection; expression of these genes is known to increase under nutrient stress. Homologs of several genes involved in anaerobic metabolism and ascorbate utilization were upregulated in vivo, suggesting that the organism is adjusting its metabolism to anaerobiosis in vivo.

ORGANISM(S): [Haemophilus] ducreyi

PROVIDER: GSE75236 | GEO | 2015/11/21

SECONDARY ACCESSION(S): PRJNA302862

REPOSITORIES: GEO

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Haemophilus ducreyi transcriptome during human infection

Project description:To better understand the molecular mechanisms underlying Haemophilus ducreyi infection in humans, here we determined the transcriptional profile of H. ducreyi in human lesions using RNA-Seq and compared it to that of in vitro growth. We were able to show that the in vivo transcriptome did not resemble that of in vitro growth. Compared to the inoculum, H. ducreyi harvested from pustules differentially expressed ~120 genes, of which 68 were upregulated. A large proportion of the upregulated genes encoded homologs of proteins involved in nutrient transport, alternative carbon pathways, growth arrest response, heat shock response, and DNA recombination. H. ducreyi upregulated few genes or operons (hgbA, flp-tad, and lspB-lspA2) required for human infection; expression of these genes is known to increase under nutrient stress. Homologs of several genes involved in anaerobic metabolism and ascorbate utilization were upregulated in vivo, suggesting that the organism is adjusting its metabolism to anaerobiosis in vivo. RNA from Haemophilus ducreyi infected pustules were collected from four volunteers and performed RNA-Seq.

2015-11-21 | E-GEOD-75236 | biostudies-arrayexpress

Haemophilus ducreyi infection induces oxidative stress, central metabolic changes, and a mixed pro- and anti-inflammatory environment in the human host

Project description:Few studies have investigated host-bacterial interactions at sites of infection in humans using transcriptomics and metabolomics. Haemophilus ducreyi causes cutaneous ulcers in children and the genital ulcer disease chancroid in adults. We developed a human challenge model in which healthy adult volunteers are infected with H. ducreyi on the upper arm until they develop pustules. Here, we characterized host-pathogen interactions in pustules using transcriptomics and metabolomics and examined interactions between the host transcriptome and metabolome using integrated omics. In a previous pilot study, we determined the human and H. ducreyi transcriptomes and the metabolome of pustule and wounded sites of 4 volunteers (B. Griesenauer, et al. mBio 10(3):e01193-19 https://doi.org/10.1128/mBio.01193-19). While we could form provisional transcriptional networks between the host and H. ducreyi, the study was underpowered to integrate the metabolome with the host transcriptome. To better define and integrate the transcriptomes and metabolome, we used samples from both the pilot study (n=4) and new volunteers (n=8) to identify 5,495 human differentially expressed genes (DEGs), 123 H. ducreyi DEGs, 205 differentially abundant positive ions, and 198 differentially abundant negative ions. We identified 42 positively correlated and 29 negatively correlated human-¬H. ducreyi transcriptome clusters. In addition, we defined human transcriptome-metabolome networks consisting of 9 total clusters, which highlighted changes in fatty acid metabolism and mitigation of oxidative damage. Taken together, the data suggests a mixed pro- and anti-inflammatory environment and rewired central metabolism in the host that provides a hostile, nutrient limited environment for H. ducreyi.

2022-11-23 | GSE214586 | GEO

Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host

Project description:A major gap in understanding infectious diseases is the lack of information about molecular interaction networks between pathogens and the human host. Haemophilus ducreyi causes the genital ulcer disease chancroid in adults and is a leading cause of cutaneous ulcers in children in the tropics. We developed a model in which human volunteers are infected on the upper arm with H. ducreyi until they develop pustules. To define the H. ducreyi and human interactome, we determined bacterial and host transcriptomic and host metabolomic changes in pustules. We found in vivo H. ducreyi transcripts were distinct from those in the inocula as were host transcripts in pustule and wounded control sites. Many of the upregulated H. ducreyi genes were involved in ascorbic acid and anaerobic metabolism and inorganic ion/nutrient transport. The top 20 significantly expressed human pathways showed that all were involved in immune responses. We generated a bipartite network for interactions between host and bacterial gene transcription; multiple positively correlated networks contained H. ducreyi genes involved in anaerobic metabolism and host genes involved with the immune response. Metabolomic studies showed that pustule and wounded samples had different metabolite compositions; the top ion pathway involved ascorbate and aldarate metabolism, which correlated with the H. ducreyi transcriptional response and upregulation of host genes involved in ascorbic acid recycling. These data show that an interactome exists between H. ducreyi and the human host and suggests that H. ducreyi exploits the metabolic niche created by the host immune response.

2019-05-30 | GSE130901 | GEO

Host Susceptibility to H. ducreyi Infection is Associated with Unique Transcript Profiles in Tissue and Dendritic Cells

Project description:Comparison of gene expression from subjects who resolved or formed pustules to H.ducreyi. In human inoculation experiments, the cutaneous immune response to Haemophilus ducreyi consists of serum, PMN, macrophages, T cells and myeloid DC. In reinfection experiments, some subjects form pustules twice (PP group) or resolve infection twice (RR group). Although pustule formation is associated with serum resistance and phagocytic failure, there are no differences in the ability of isolated phagocytes or serum obtained from PP and RR subjects to ingest or kill H. ducreyi. To identify the basis for differential host susceptibility to H. ducreyi, we used microarrays to profile gene expression in infected and uninfected tissue and monocyte-derived DC obtained from PP and RR subjects. In infected tissue, both groups had a core response to H. ducreyi. Many additional transcripts that signify active immune function were upregulated exclusively in RR tissue, while PP tissue exclusively contained differentially regulated transcripts consistent with immune dysregulation. The core response of infected DC from both groups was typical of a DC1 response. RR DC exclusively expressed many additional transcripts indicative of DC1 function, while PP DC uniquely expressed differentially regulated transcripts characteristic of both DC1 and DCreg. The data suggest that DC from PP and RR subjects are prewired to respond differentially to H. ducreyi. Keywords: comparison of two phenotypes, resolver and pustule former

2007-09-13 | GSE5547 | GEO

Genes differentially expressed by Haemophilus ducreyi during anaerobic growth significantly overlap with those differentially expressed during experimental infection of human volunteers

Project description:The transcriptional response of Haemophilus ducreyi to anaerobiosis was determined over the course of 18 h. Cells were collected from aerobic and anaerobic cultures at 4, 8, or 18 hours .

2022-03-28 | GSE193250 | GEO

Transcriptomes of 35000HP, ÎcpxA, ÎcpxR mutant strains of Haemophilus ducreyi in mid-log, transition, and stationary phase

Project description:To better understand the role of H. ducreyi CpxRA in controlling virulence determinants, here we defined genes potentially regulated by CpxRA by using RNA-Seq. Activation of CpxR by deletion of cpxA repressed nearly 70% of its targets, including seven established virulence determinants. Inactivation of CpxR by deletion of cpxR differentially regulated few genes and increased the expression of one virulence determinant. We identified a CpxR binding motif that was enriched in downregulated but not upregulated targets. These data reinforce the hypothesis that CpxA phosphatase activity plays a critical role in controlling H. ducreyi virulence in vivo. Characterization of the downregulated genes may offer new insights into pathogenesis. RNA of Haemophilus ducreyi wildtype, cpxA and cpxR mutants were collected at mid-log, transition, and stationary phases of growth, in quadruplicate.

2015-11-21 | E-GEOD-75237 | biostudies-arrayexpress

Haemophilus ducreyi infection induces oxidative stress, central metabolic changes, and a mixed pro- and anti-inflammatory environment in the human host

Project description:Few studies have investigated host-bacterial interactions at sites of infection in humans using transcriptomics and metabolomics. Haemophilus ducreyi causes cutaneous ulcers in children and the genital ulcer disease chancroid in adults. We developed a human challenge model in which healthy adult volunteers are infected with H. ducreyi on the upper arm until they develop pustules. Here, we characterized host-pathogen interactions in pustules using transcriptomics and metabolomics and examined interactions between the host transcriptome and metabolome using integrated omics. In a previous pilot study, we determined the human and H. ducreyi transcriptomes and the metabolome of pustule and wounded sites of 4 volunteers (B. Griesenauer, et al. mBio 10(3):e01193-19 https://doi.org/10.1128/mBio.01193-19). While we could form provisional transcriptional networks between the host and H. ducreyi, the study was underpowered to integrate the metabolome with the host transcriptome. To better define and integrate the transcriptomes and metabolome, we used samples from both the pilot study (n=4) and new volunteers (n=8) to identify 5,495 human differentially expressed genes (DEGs), 123 H. ducreyi DEGs, 205 differentially abundant positive ions, and 198 differentially abundant negative ions. We identified 42 positively correlated and 29 negatively correlated human-H. ducreyi transcriptome clusters. In addition, we defined human transcriptome-metabolome networks consisting of 9 total clusters, which highlighted changes in fatty acid metabolism and mitigation of oxidative damage. Taken together, the data suggest a mixed pro- and anti-inflammatory environment and rewired central metabolism in the host that provides a hostile, nutrient limited environment for H. ducreyi.

2022-11-01 | MSV000090626 | MassIVE

H. ducreyi 35000HP grown in the presence or absence of FCS

Project description:Haemophilus ducreyi 35000HP was subjected to different in vitro growth conditions that resemble the in vivo host environment (presence of serum), in order to ascertain the overall changes in gene expression. This information might identify genes important for colonization and/or survival inside the host.

2009-12-05 | GSE13851 | GEO

RpoE-dependent transcriptomes of Haemophilus ducreyi

Project description:To potentially understand how H. ducreyi responds to membrane stress, here we defined RpoE-dependent genes using RNA-Seq. We identified 180 RpoE-dependent genes, of which 98% were upregulated; a major set of these genes encodes homologues of envelope maintenance and repair factors. We also identified and validated a putative RpoE promoter consensus sequence, which was enriched in the majority of RpoE-dependent targets. Comparison of RpoE-dependent genes to those controlled by CpxR showed that each transcription factor regulated a distinct set of genes. Given that RpoE activated a large number of genes encoding envelope maintenance and repair factors and CpxRA represses genes encoding envelope-localized proteins, these data suggest that RpoE and CpxRA appear to play distinct yet complementary roles in regulating envelope homeostasis in H. ducreyi. RNA of Haemophilus ducreyi 35000HP wild-type strain containing a rpoE inducible plasmid and wild-type strain containing a control plasmid were collected at 0 minutes, 5 minutes, and 10 minutes after induction in quadruplicate.

2015-11-21 | E-GEOD-75238 | biostudies-arrayexpress

RpoE-dependent transcriptomes of Haemophilus ducreyi

2015-11-21 | GSE75238 | GEO

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