Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection.
Abstract
Chlamydia trachomatis, an obligate intracellular bacterium with limited metabolic
capabilities, possesses the futalosine pathway for menaquinone biosynthesis. Futalosine
pathway enzymes have promise as narrow-spectrum antibiotic targets, but the activity
and essentiality of chlamydial menaquinone biosynthesis have yet to be established.
In this work, menaquinone-7 (MK-7) was identified as a C. trachomatis-produced quinone
through liquid chromatography-tandem mass spectrometry. An immunofluorescence-based
assay revealed that treatment of C. trachomatis-infected HeLa cells with the futalosine
pathway inhibitor docosahexaenoic acid (DHA) reduced inclusion number, inclusion size,
and infectious progeny. Supplementation with MK-7 nanoparticles rescued the effect
of DHA on inclusion number, indicating that the futalosine pathway is a target of
DHA in this system. These results open the door for menaquinone biosynthesis inhibitors
to be pursued in antichlamydial development.
Type
Journal articleSubject
Hela CellsInclusion Bodies
Humans
Chlamydia trachomatis
Chlamydia Infections
Vitamin K 2
Nucleosides
Docosahexaenoic Acids
Anti-Bacterial Agents
Automation
Nanoparticles
Biosynthetic Pathways
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https://hdl.handle.net/10161/24484Published Version (Please cite this version)
10.1002/1873-3468.14223Publication Info
(2021). Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia
trachomatis infection. FEBS letters, 595(24). pp. 2995-3005. 10.1002/1873-3468.14223. Retrieved from https://hdl.handle.net/10161/24484.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Dewey G. McCafferty
Professor of Chemistry
Our research interests are broadly based in chemical biology, mechanistic enzymology
and molecular medicine. Towards this end our group is engaged in understanding the
chemical and kinetic mechanisms, substrate specificity and therapeutic importance
of enzymes that posttranslationally modify chromatin, such as histone deacetylases,
histone demethylases, histone methyl transferases, and chromatin assembly and remodeling
complexes. Building on a mechanistic foundation, our laboratory is also int
David Needham
Professor in the Department of Mechanical Engineering and Materials Science
Professor Needham has been at Duke since 1987 and over the years has developed many
collaborative and scholarly relationships across the campus and Medical School. He
holds Faculty and membership appointments as: Associate Professor of Biomedical Engineering;
Center for Bioinspired Materials and Material Systems; Center for Biomolecular and
Tissue Engineering; Duke Comprehensive Cancer Center; and the Duke Cancer Institute.
Internationally, he holds a joint appointment as Professor of T
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