Cited by 151Tuberculosis Research and EpidemiologyBacterial Genetics and BiotechnologyInfectious Diseases and Tuberculosis

Menaquinone synthesis is critical for maintaining mycobacterial viability during exponential growth and recovery from non‐replicating persistence

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Dhiman, Rakesh K., Mahapatra, Sebabrata, Slayden, Richard A., Boyne, Melissa E., Lenaerts, Anne, Hinshaw, Jerald C., Angala, Shiva K., Chatterjee, Delphi +4 more·2009·Molecular Microbiology

Abstract

Summary: Understanding the basis of bacterial persistence in latent infections is critical for eradication of tuberculosis. Analysis of Mycobacterium tuberculosis mRNA expression in an in vitro model of non‐replicating persistence indicated that the bacilli require electron transport chain components and ATP synthesis for survival. Additionally, low μM concentrations of aminoalkoxydiphenylmethane derivatives inhibited both the aerobic growth and survival of non‐replicating, persistent M. tuberculosis. Metabolic labelling studies and quantification of cellular menaquinone levels suggested that menaquinone synthesis, and consequently electron transport, is the target of the aminoalkoxydiphenylmethane derivatives. This hypothesis is strongly supported by the observations that treatment with these compounds inhibits oxygen consumption and that supplementation of growth medium with exogenous menaquinone rescued both growth and oxygen consumption of treated bacilli. In vitro assays indicate that the aminoalkoxydiphenylmethane derivatives specifically inhibit MenA, an enzyme involved in the synthesis of menaquinone. Thus, the results provide insight into the physiology of mycobacterial persistence and a basis for the development of novel drugs that enhance eradication of persistent bacilli and latent tuberculosis.

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Crossref · 10.1111/j.1365-2958.2009.06625.x

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Research works printed but not linked: 2

  1. Gennis RB Stewart V 1996 Respiration Eschericia coli and Salmonella Neidhardt FC Washington, D.C. ASM Press 217 261
  2. Minnikin DE 1982 Lipids: complex lipids, their chemistry, biosynthesis and roles The Biology of Mycobacteria Ratledge C Stanford J London Academic Press 95 184

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Authors
Dhiman, R. K., Mahapatra, S., Slayden, R. A., Boyne, M. E., Lenaerts, A., Hinshaw, J. C., Angala, S. K., Chatterjee, D., Biswas, K., Narayanasamy, P., Kurosu, M., & Crick, D. C.
Affiliations
  • Colorado State University (US)
  • University of Utah (US)
Corresponding author
Crick, Dean C.
Venue
Molecular Microbiology
Publisher
Wiley
Published
2009-03-19
Volume
72
Issue
1
Pages
85-97
ISSN
  • 0950-382X (ISSN-L)
  • 1365-2958
OpenAlex
W2152545013
Cited by
146
References
49
Citations by year
2026: 5 · 2025: 5 · 2024: 7 · 2023: 10 · 2022: 6 · 2021: 6 · 2020: 11 · 2019: 11 · 2018: 7 · 2017: 11 · 2016: 10 · 2015: 12 · 2014: 14 · 2013: 5 · 2012: 7
FWCI
5.98
Type
journal article
Language
en
Open access
Locations
  • Molecular Microbiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R56AI049151, R01AI055298, AI049151, AI-06357, P01AI057836, R01AI049151, AI055298, AI057836)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
Keywords
Mycobacterium tuberculosis, non-replicating persistence, latent tuberculosis infection, Middle East and North Africa, electron transport chain, oxygen consumption, bacterial persistence, tuberculosis drug development
MeSH terms
Adenosine Triphosphate, Mycobacterium tuberculosis, Oxygen Consumption, RNA, Bacterial, RNA, Messenger, Gene Expression Regulation, Bacterial, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Vitamin K 2, Electron Transport Chain Complex Proteins, Microbial Viability

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