The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Menaquinone synthesis is critical for maintaining mycobacterial viability during exponential growth and recovery from non‐replicating persistence
Open accessAbstract
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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“Because it has recently been shown that both the electron transport system and ATP synthesis are viable anti-TB drug targets (Andries et al., 2005; Weinstein et al., 2005) it was hypothesized that menaquinone synthesis could be critical for mycobacterial survival and the following studies were…”
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Metadata
- 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.
- ORCID
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2009-03-19
- Volume
- 72
- Issue
- 1
- Pages
- 85-97
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- PMC
- PMC4747042
- 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
- green
- www.ncbi.nlm.nih.gov
- 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 › Infectious Diseases › 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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