Drug Repurposing of Bromodomain Inhibitors as Potential Novel Therapeutic Leads for Lymphatic Filariasis Guided by Multispecies Transcriptomics-Reference-Cited by-同舟云学术

Drug Repurposing of Bromodomain Inhibitors as Potential Novel Therapeutic Leads for Lymphatic Filariasis Guided by Multispecies Transcriptomics

Published:2019-12-17 Issue:6 Volume:4 Page:
ISSN:2379-5077
Container-title:mSystems
language:en
Short-container-title:mSystems

Author:

Chung Matthew¹²^ORCID,Teigen Laura E.³,Libro Silvia⁴,Bromley Robin E.¹^ORCID,Olley Dustin¹,Kumar Nikhil¹,Sadzewicz Lisa¹,Tallon Luke J.¹,Mahurkar Anup¹,Foster Jeremy M.⁴,Michalski Michelle L.³,Dunning Hotopp Julie C.¹²⁵^ORCID

Affiliation:

1. Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA

2. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA

3. Department of Biology, University of Wisconsin Oshkosh, Oshkosh, Wisconsin, USA

4. New England Biolabs, Ipswich, Massachusetts, USA

5. Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, USA

Abstract

The current treatment regimen for lymphatic filariasis is mostly microfilaricidal. In an effort to identify new drug candidates for lymphatic filariasis, we conducted a three-way transcriptomics/systems biology study of one of the causative agents of lymphatic filariasis, Brugia malayi , its Wolbachia endosymbiont w Bm, and its vector host Aedes aegypti at 16 distinct B. malayi life stages. B. malayi upregulates the expression of bromodomain-containing proteins in the adult female, embryo, and microfilaria stages. In vitro , we find that the existing cancer therapeutic JQ1(+), which is a bromodomain and extraterminal protein inhibitor, has adulticidal activity in B. malayi .

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Computer Science Applications,Genetics,Molecular Biology,Modelling and Simulation,Ecology, Evolution, Behavior and Systematics,Biochemistry,Physiology,Microbiology

Link

https://journals.asm.org/doi/pdf/10.1128/mSystems.00596-19

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