An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms

Thomas M Hart¹, Nicole D Sonnert², Xiaotian Tang¹, Reetika Chaurasia¹, Paige E Allen³, Jason R Hunt³, Curtis B Read³, Emily E Johnson⁴, Gunjan Arora¹, Yile Dai⁵, Yingjun Cui¹, Yu-Min Chuang¹, Qian Yu¹, M Sayeedur Rahman⁶, M Tays Mendes⁶, Agustin Rolandelli⁶, Pallavi Singh¹, Abhai K Tripathi⁷, Choukri Ben Mamoun⁸, Melissa J Caimano⁹, Justin D Radolf¹⁰, Yi-Pin Lin¹¹, Volker Fingerle¹², Gabriele Margos¹², Utpal Pal¹³, Raymond M Johnson⁸, Joao H F Pedra⁶, Abdu F Azad⁶, Jeanne Salje¹⁴, George Dimopoulos⁷, Joseph M Vinetz¹⁵, Jason A Carlyon¹⁶, Noah W Palm¹⁷, Erol Fikrig¹⁸, Aaron M Ring¹⁹

Affiliations

¹ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
² Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06510, USA.
³ Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
⁴ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Epidemiology and Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA.
⁵ Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510, USA.
⁶ Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁷ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
⁸ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06510, USA.
⁹ Department of Medicine, UConn Health, Farmington, CT 06030, USA; Department of Pediatrics, UConn Health, Farmington, CT 06030, USA; Department of Molecular Biology and Biophysics, UConn Health, Farmington, CT 06030, USA.
¹⁰ Department of Medicine, UConn Health, Farmington, CT 06030, USA; Department of Pediatrics, UConn Health, Farmington, CT 06030, USA; Department of Molecular Biology and Biophysics, UConn Health, Farmington, CT 06030, USA; Department of Genetics and Genome Sciences, UConn Health, Farmington, CT 06030, USA; Department of Immunology, UConn Health, Farmington, CT 06030, USA.
¹¹ Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
¹² Bavarian Health and Food Safety Authority, Oberschleißheim, Munich 85764, Bavaria, Germany.
¹³ Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
¹⁴ Department of Pathology, University of Cambridge, Cambridge CB2 1TN, UK; Department of Biochemistry, University of Cambridge, Cambridge CB2 1TN, UK.
¹⁵ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación Y Desarrollo, Facultad de Ciencias Y Filosofia, Universidad Peruana Cayetano Heredia, Lima 15102, Peru; Instituto de Medicina Tropical Alexander Von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15102, Peru.
¹⁶ Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA. Electronic address: jason.carlyon@vcuhealth.org.
¹⁷ Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: noah.palm@yale.edu.
¹⁸ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: erol.fikrig@yale.edu.
¹⁹ Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98102, USA. Electronic address: aaronring@fredhutch.org.

PMID: 38876107
DOI: 10.1016/j.cell.2024.05.023

An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms

Thomas M Hart et al. Cell. 2024.

. 2024 Jun 11:S0092-8674(24)00532-4.

doi: 10.1016/j.cell.2024.05.023. Online ahead of print.

Authors

Affiliations

¹ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
² Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06510, USA.
³ Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
⁴ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Epidemiology and Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA.
⁵ Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510, USA.
⁶ Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁷ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
⁸ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06510, USA.
⁹ Department of Medicine, UConn Health, Farmington, CT 06030, USA; Department of Pediatrics, UConn Health, Farmington, CT 06030, USA; Department of Molecular Biology and Biophysics, UConn Health, Farmington, CT 06030, USA.
¹⁰ Department of Medicine, UConn Health, Farmington, CT 06030, USA; Department of Pediatrics, UConn Health, Farmington, CT 06030, USA; Department of Molecular Biology and Biophysics, UConn Health, Farmington, CT 06030, USA; Department of Genetics and Genome Sciences, UConn Health, Farmington, CT 06030, USA; Department of Immunology, UConn Health, Farmington, CT 06030, USA.
¹¹ Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA.
¹² Bavarian Health and Food Safety Authority, Oberschleißheim, Munich 85764, Bavaria, Germany.
¹³ Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
¹⁴ Department of Pathology, University of Cambridge, Cambridge CB2 1TN, UK; Department of Biochemistry, University of Cambridge, Cambridge CB2 1TN, UK.
¹⁵ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Laboratorio ICEMR-Amazonia, Laboratorios de Investigación Y Desarrollo, Facultad de Ciencias Y Filosofia, Universidad Peruana Cayetano Heredia, Lima 15102, Peru; Instituto de Medicina Tropical Alexander Von Humboldt, Universidad Peruana Cayetano Heredia, Lima 15102, Peru.
¹⁶ Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA. Electronic address: jason.carlyon@vcuhealth.org.
¹⁷ Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: noah.palm@yale.edu.
¹⁸ Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: erol.fikrig@yale.edu.
¹⁹ Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA 98102, USA. Electronic address: aaronring@fredhutch.org.

PMID: 38876107
DOI: 10.1016/j.cell.2024.05.023

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.

Keywords: Lyme disease; arthropod-borne disease; host sensing; host-pathogen interactions; infectious disease; mechanisms of pathogenicity; protein disulfide isomerase; systems biology; thioredoxin; vector-borne disease.

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Conflict of interest statement

Declaration of interests N.W.P. and A.M.R. are inventors of a patent describing the BASEHIT technique.

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An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms

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An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms

Authors

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Abstract

Conflict of interest statement

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Abstract

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