A Parallel Adder Coordinates Mycobacterial Cell-Cycle Progression and Cell-Size Homeostasis in the Context of Asymmetric Growth and Organization
Open accessAbstract
In model bacteria, such as E. coli and B. subtilis, regulation of cell-cycle progression and cellular organization achieves consistency in cell size, replication dynamics, and chromosome positioning [1-3]. Mycobacteria elongate and divide asymmetrically, giving rise to significant variation in cell size and elongation rate among closely related cells [4, 5]. Given the physical asymmetry of mycobacteria, the models that describe coordination of cellular organization and cell-cycle progression in model bacteria are not directly translatable [1, 2, 6-8]. Here, we used time-lapse microscopy and fluorescent reporters of DNA replication and chromosome positioning to examine the coordination of growth, division, and chromosome dynamics at a single-cell level in Mycobacterium smegmatis (M. smegmatis) and Mycobacterium bovis Bacillus Calmette-Guérin (BCG). By analyzing chromosome and replisome localization, we demonstrated that chromosome positioning is asymmetric and proportional to cell size. Furthermore, we found that cellular asymmetry is maintained throughout the cell cycle and is not established at division. Using measurements and stochastic modeling of mycobacterial cell size and cell-cycle timing in both slow and fast growth conditions, we found that well-studied models of cell-size control are insufficient to explain the mycobacterial cell cycle. Instead, we showed that mycobacterial cell-cycle progression is regulated by an unprecedented mechanism involving parallel adders (i.e., constant growth increments) that start at replication initiation. Together, these adders enable mycobacterial populations to regulate cell size, growth, and heterogeneity in the face of varying environments.
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Mycobacteria divide asymmetrically by a fast, mechanical-snapping mechanism.
“Mycobacteria divide asymmetrically by a fast, mechanical-snapping mechanism (107, 118–121).”
From Mycobacterium smegmatis: The Vanguard of Mycobacterial Research (2023) · cites this paper as [120]
The Abstract and Results and Discussion describe asymmetric mycobacterial division. STAR Methods identifies snapping or pinching as observable division events, but does not establish that division is fast or explain snapping as a mechanical mechanism. Page numbers are unavailable in our copy. (LLM, conf=0.84)
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- Authors
- Logsdon, M. M., Ho, P.-Y., Papavinasasundaram, K., Richardson, K., Cokol, M., Sassetti, C. M., Amir, A., & Aldridge, B. B.
- Affiliations
- Tufts University (US)
- Harvard University (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Aldridge, Bree B.
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 27
- Issue
- 21
- Pages
- 3367-3374.e7
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC5687851
- OpenAlex
- W2766834052
- Cited by
- 69
- References
- 32
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 3 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 13
- FWCI
- 5.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- Alfred P. Sloan Foundation
- NIH (1DP2LM011952-01, P50 GM107618-01A1, AI064282, 5T32AI007422-24)
- Harvard Dean’s Competitive Fund for Promising Scholarship
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Keywords
- parallel adder, cell size homeostasis, cell cycle progression, asymmetric cell division, Mycobacterium smegmatis, Mycobacterium bovis BCG, chromosome positioning, replisome, DNA replication, cell growth, stochastic modeling, cell size control, single-cell dynamics
- MeSH terms
- Cell Cycle, Chromosomes, Bacterial, DNA Replication, Mycobacterium bovis, Mycobacterium smegmatis, Cell Size, Time-Lapse Imaging, Asymmetric Cell Division
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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