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| Status |
Public on Nov 23, 2022 |
| Title |
Haemophilus ducreyi infection induces oxidative stress, central metabolic changes, and a mixed pro- and anti-inflammatory environment in the human host |
| Organisms |
[Haemophilus] ducreyi; Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Eight human volunteers were infected with H. ducreyi on the upper arm. To control for delivery of the bacteria via puncture wounds in the skin, a wounded control sample that delivered PBS only was also performed for each person. To control for changes in bacterial gene expression, the bacterial cultures (4) used to inoculate the volunteers were collected. All samples were processed for RNA-seq. We compared the differential expression of human genes in pustules v. wounds and the differential expression of in vivo v. cultured bacterial genes.
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| Contributor(s) |
Brothwell JA, Spinola SM |
| Citation(s) |
36453940 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI137116 |
Determination of the Interactome between Haemophilus ducreyi and the Human Host. |
INDIANA UNIVERSITY |
Stanley M. Spinola |
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| Submission date |
Oct 01, 2022 |
| Last update date |
Jan 11, 2023 |
| Contact name |
Julie Brothwell |
| E-mail(s) |
jbrothwe@iu.edu
|
| Phone |
3172781027
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| Organization name |
Indiana University
|
| Department |
Department of Microbiology & Immunology
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| Street address |
635 Barnhill Dr., MS420
|
| City |
Indianapolis |
| State/province |
IN |
| ZIP/Postal code |
46202 |
| Country |
USA |
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| Platforms (3) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
| GPL31188 |
Illumina NovaSeq 6000 ([Haemophilus] ducreyi) |
| GPL32713 |
Illumina NovaSeq 6000 ([Haemophilus] ducreyi; Homo sapiens) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA886051 |
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