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Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection.

Publication ,  Journal Article
Dudiak, BM; Nguyen, TM; Needham, D; Outlaw, TC; McCafferty, DG
Published in: FEBS letters
December 2021

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.

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Published In

FEBS letters

DOI

EISSN

1873-3468

ISSN

0014-5793

Publication Date

December 2021

Volume

595

Issue

24

Start / End Page

2995 / 3005

Related Subject Headings

  • Vitamin K 2
  • Nucleosides
  • Nanoparticles
  • Inclusion Bodies
  • Humans
  • Hela Cells
  • HeLa Cells
  • Docosahexaenoic Acids
  • Chlamydia trachomatis
  • Chlamydia Infections
 

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Dudiak, B. M., Nguyen, T. M., Needham, D., Outlaw, T. C., & McCafferty, D. G. (2021). Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection. FEBS Letters, 595(24), 2995–3005. https://doi.org/10.1002/1873-3468.14223
Dudiak, Brianne M., Tri M. Nguyen, David Needham, Taylor C. Outlaw, and Dewey G. McCafferty. “Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection.FEBS Letters 595, no. 24 (December 2021): 2995–3005. https://doi.org/10.1002/1873-3468.14223.
Dudiak BM, Nguyen TM, Needham D, Outlaw TC, McCafferty DG. Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection. FEBS letters. 2021 Dec;595(24):2995–3005.
Dudiak, Brianne M., et al. “Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection.FEBS Letters, vol. 595, no. 24, Dec. 2021, pp. 2995–3005. Epmc, doi:10.1002/1873-3468.14223.
Dudiak BM, Nguyen TM, Needham D, Outlaw TC, McCafferty DG. Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection. FEBS letters. 2021 Dec;595(24):2995–3005.
Journal cover image

Published In

FEBS letters

DOI

EISSN

1873-3468

ISSN

0014-5793

Publication Date

December 2021

Volume

595

Issue

24

Start / End Page

2995 / 3005

Related Subject Headings

  • Vitamin K 2
  • Nucleosides
  • Nanoparticles
  • Inclusion Bodies
  • Humans
  • Hela Cells
  • HeLa Cells
  • Docosahexaenoic Acids
  • Chlamydia trachomatis
  • Chlamydia Infections