# Determination of the Interactome between Haemophilus ducreyi and the Human Host.

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $652,388

## Abstract

A major gap in our understanding of infectious diseases is the lack of information about molecular interaction
networks between an infecting pathogen and the human host, which has yet to be accomplished for a bacterial
infection in humans. The purpose of this application is to define an interactome on a transcript level for the
primary skin pathogen, Haemophilus ducreyi (HD), in experimentally infected human volunteers using RNA
sequencing (RNA-seq) and metabolomics. HD causes chancroid, a genital ulcer (GU) disease that facilitates
HIV transmission and is as a major cause of cutaneous ulcers (CU) in children in yaws-endemic countries.
Efforts to eradicate HD-associated CU with antibiotics failed due to environmental reservoirs. To study the
biology of HD, we developed a model in which the HD GU strain 35000HP and its derivatives are inoculated
into the skin of the upper arm of adult volunteers. Whole genome sequencing shows that most CU strains are
nearly identical to 35000HP, indicating that our model is highly relevant to GU and CU. In the model and in
natural chancroid, HD resides in an abscess where it is surrounded by polymorphonuclear leukocytes and
macrophages and remains extracellular by evading phagocytosis. In our new preliminary data, we show
that an interaction network exists between HD and the host and that differential host and bacterial transcript
expression correlates with metabolomic changes at infected vs. wounded sites. HD primarily upregulates the
expression of genes involved in adapting to anaerobiosis and uptake and utilization of metal ions and
alternative carbon sources, such as ascorbic acid, consistent with the idea of “nutritional virulence.” Our new
metabolomics data show that ascorbic acid pathways are upregulated in lesions. Thus, we hypothesize that
the host regulates its gene transcription to phagocytize and limit nutrients to HD, that HD regulates its
gene transcription to counteract these host defenses, that host gene expression correlates with
metabolomic profiles at infected sites, and that bacterial genes that are involved in adaptation to the
metabolic niche created by the host response will be required for virulence. Our specific aims are 1) to
define the metabolome and the interactome between HD and the human host in infected tissue and to
correlate the host transcriptional response to metabolic changes in lesions; 2) to identify the cells responsible
for the host transcriptional response using single cell RNA-seq; 3) to determine whether the HD genes
involved in exploitation of the host niche are required for virulence in humans and the mechanism(s) by which
these genes contribute to virulence. The importance of this study is that we will be the first to determine an
interactome at a site of a bacterial human infection, define the host cells responsible for the transcriptional
response, correlate the host response to metabolomic changes in lesions, and study how HD exploits these
metabolites. We will prov...

## Key facts

- **NIH application ID:** 9885152
- **Project number:** 1R01AI137116-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Stanley M. Spinola
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $652,388
- **Award type:** 1
- **Project period:** 2019-12-17 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9885152

## Citation

> US National Institutes of Health, RePORTER application 9885152, Determination of the Interactome between Haemophilus ducreyi and the Human Host. (1R01AI137116-01A1). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9885152. Licensed CC0.

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