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Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection.
- Source :
-
FEBS letters [FEBS Lett] 2021 Dec; Vol. 595 (24), pp. 2995-3005. Date of Electronic Publication: 2021 Nov 16. - Publication Year :
- 2021
-
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.<br /> (© 2021 Federation of European Biochemical Societies.)
- Subjects :
- Anti-Bacterial Agents chemistry
Anti-Bacterial Agents pharmacology
Automation
Chlamydia Infections microbiology
Docosahexaenoic Acids pharmacology
HeLa Cells
Humans
Inclusion Bodies drug effects
Inclusion Bodies metabolism
Nanoparticles chemistry
Nucleosides chemistry
Vitamin K 2 chemistry
Vitamin K 2 metabolism
Biosynthetic Pathways drug effects
Chlamydia Infections pathology
Chlamydia trachomatis physiology
Nucleosides biosynthesis
Vitamin K 2 analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3468
- Volume :
- 595
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- FEBS letters
- Publication Type :
- Academic Journal
- Accession number :
- 34741525
- Full Text :
- https://doi.org/10.1002/1873-3468.14223