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Role of Mycobacterium tuberculosis Ser/Thr Kinase PknF: Implications in Glucose Transport and Cell Division
Open accessAbstract
Protein kinases have a diverse array of functions in bacterial physiology, with a distinct role in the regulation of development, stress responses, and pathogenicity. pknF, one of the 11 kinases of Mycobacterium tuberculosis, encodes an autophosphorylating, transmembrane serine/threonine protein kinase, which is absent in the fast-growing, nonpathogenic Mycobacterium smegmatis. Herein, we investigate the physiological role of PknF using an antisense strategy with M. tuberculosis and expressing PknF and its kinase mutant (K41M) in M. smegmatis. Expression of PknF in M. smegmatis led to reduction in the growth rate and shortening and swelling of cells with constrictions. Interestingly, an antisense strain of M. tuberculosis expressing a low level of PknF displayed fast growth and a deformed cell morphology compared to the wild-type strain. Electron microscopy showed that most of the cells of the antisense strain were of a smaller size with an aberrant septum. Furthermore, nutrient transport analysis of these strains was conducted using 3H-labeled and 14C-labeled substrates. A significant increase in the uptake of D-glucose but not of glycerol, leucine, or oleic acid was observed in the antisense strain compared to the wild-type strain. The results suggest that PknF plays a direct/indirect role in the regulation of glucose transport, cell growth, and septum formation in M. tuberculosis.
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As these STPKs are associated with stasis conditions, their phosphorylation of FAS-II enzymes reduces mycolic acid synthesis during stasis and chronic phases of infection.
“As these STPKs are associated with stasis conditions14,72,94,95, we predict that their phosphorylation of FAS-II enzymes reduces mycolic acid synthesis during stasis and chronic phases of infection.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [94]
PknF inhibits PcaA by phosphorylating it, which may help to enforce dormancy in the chronic phase.
“PknF inhibits PcaA by phosphorylating it96, which may help to enforce dormancy in the chronic phase94.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [94]
Because PknF function has been associated with growth restriction, this inhibition of KasB is expected to occur during stasis, and it may help decrease bacterial growth and modulate pathogenesis.
“Because PknF function has been associated with growth restriction94, we expect this inhibition of KasB to occur during stasis, and it may help decrease bacterial growth and modulate pathogenesis.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [94]
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Bacterial Growth and Cell Division: a Mycobacterial Perspective
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The mycobacterial cell envelope — a moving target
Dulberger, C. L., Rubin, E. J., & Boutte, C. C. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0273-7 · Cited by 365
Metadata
- Authors
- Deol, P., Vohra, R., Saini, A. K., Singh, A., Chandra, H., Chopra, P., Das, T. K., Tyagi, A. K., & Singh, Y.
- Affiliations
- Institute of Genomics and Integrative Biology (IN)
- University of Delhi (IN)
- All India Institute of Medical Sciences (IN)
- Corresponding author
- Singh, Yogendra
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2005-05-15
- Volume
- 187
- Issue
- 10
- Pages
- 3415-3420
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC1112024
- OpenAlex
- W1992055692
- Cited by
- 99
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 10 · 2013: 5 · 2012: 6
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Bacteriology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research, India
- 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 › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- Mycobacterium tuberculosis, serine/threonine kinase, glucose transport, cell division, septum formation, cell morphology, antisense gene expression, Mycobacterium smegmatis, bacterial growth rate, nutrient uptake
- MeSH terms
- Carbon Radioisotopes, Cell Division, Cell Wall, Glucose, Microscopy, Electron, Scanning, Mycobacterium tuberculosis, Tritium, Gene Expression Regulation, Bacterial, Gene Expression Regulation, Enzymologic, RNA, Antisense, Protein Serine-Threonine Kinases, Mycobacterium smegmatis, Microscopy, Electron, Transmission
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