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Updated: Jun 23, 2025
Tick Microbiome Characterization by Next-Generation 16S rRNA Amplicon Sequencing
Published on: August 25, 2018
An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms
Thomas M Hart1, Nicole D Sonnert2, Xiaotian Tang1
1Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
Abstract:
Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens. The resulting atlas revealed 1,303 putative interactions, including hundreds of pairings with potential roles in pathogenesis, including cell invasion, tissue colonization, immune evasion, and host sensing. Subsequent functional investigations uncovered that Lyme disease spirochetes recognize epidermal growth factor as an environmental cue of transcriptional regulation and that conserved interactions between intracellular pathogens and thioredoxins facilitate cell invasion. In summary, this interactome atlas provides molecular-level insights into microbial pathogenesis and reveals potential host-directed targets for next-generation therapeutics.
Insights
This study maps pathogen interactions with human proteins to understand vector-borne diseases. It reveals new targets for developing next-generation therapeutics against infectious diseases.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Vector-borne diseases cause significant global mortality, highlighting an unmet medical need.
- Host-pathogen interactions at the extracellular protein level are critical in disease development.
Purpose of the Study:
- To create a comprehensive atlas of microbial interactions with the human exoproteome.
- To identify potential molecular targets for novel therapeutic strategies against vector-borne pathogens.
Main Methods:
- Utilized bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT).
- Interrogated interactions between 82 human-pathogen samples and 3,324 human exoproteins.
- Conducted functional investigations on identified interactions.
Main Results:
- Generated an atlas of 1,303 putative host-pathogen interactions.
- Identified hundreds of interactions potentially involved in cell invasion, colonization, immune evasion, and host sensing.
- Discovered that Lyme disease spirochetes use epidermal growth factor for transcriptional regulation and that pathogen-thioredoxin interactions aid cell invasion.
Conclusions:
- The interactome atlas provides molecular insights into microbial pathogenesis.
- Identified potential host-directed targets for next-generation therapeutics against vector-borne diseases.
