Asymmetry and Aging of Mycobacterial Cells Lead to Variable Growth and Antibiotic Susceptibility
Open accessAbstract
Live Fast, Die Faster: Treatment of Mycobacterium tuberculosis infections is complicated by the need for a prolonged course of antibiotics to fully eliminate all the bacteria present in an infected individual. Most antibiotics target growth and division machinery; thus, Aldridge et al. (p. 100 , published online 15 November) postulated that heterogeneity in the growth properties of mycobacterial cells underlies variable antibiotic susceptibility. Cell division in mycobacteria was found to be asymmetrical, with one cell inheriting the growing pole and elongating rapidly, while the other cell elongated more slowly. Over multiple cell divisions, the rapidly growing cells became more susceptible to antibiotic treatment, helping to explain the observed heterogeneity in response to antibiotic therapy.
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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 [118]
The passage describing the division-symmetry comparison (section labeled Abstract; page unavailable) reports asymmetric division in M. smegmatis and similar asymmetry in M. tuberculosis. The passages describing daughter-cell growth differences support the asymmetry component, but the copy does not describe division as fast or as occurring through mechanical snapping; searches for those terms found no supporting passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMycobacteria lack MreB and deposit new cell wall material asymmetrically at the tips of the bacilli.
“Mycobacteria lack MreB and deposit new cell wall material asymmetrically at the tips of the bacilli26,27.”
From The mycobacterial cell envelope — a moving target (2020) · cites this paper as [26]
The passage indexed as Abstract (page unavailable) reports that mycobacteria elongate at their poles, preferentially at the old pole, and describes asymmetric cell-wall labeling. It does not say that mycobacteria lack MreB; its statement that they lack molecular rulers for symmetric division does not establish that specific claim. (LLM, conf=0.87)
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- Authors
- Aldridge, B. B., Fernandez-Suarez, M., Heller, D., Ambravaneswaran, V., Irimia, D., Toner, M., & Fortune, S. M.
- Affiliations
- Harvard University (US)
- Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
- Center for Engineering in Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
- Massachusetts General Hospital (US)
- Corresponding author
- Aldridge, Bree B.
- Fortune, Sarah M.
- Venue
- Science
- Published
- 2012-01-06
- Volume
- 335
- Issue
- 6064
- Pages
- 100-104
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3397429
- OpenAlex
- W2110760619
- Cited by
- 454
- References
- 33
- Citations by year
- 2026: 25 · 2025: 32 · 2024: 33 · 2023: 28 · 2022: 35 · 2021: 30 · 2020: 25 · 2019: 31 · 2018: 38 · 2017: 36 · 2016: 25 · 2015: 32 · 2014: 33 · 2013: 25 · 2012: 24
- FWCI
- 16.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering (P41 EB002503)
- National Institutes of Health (1DP20D001378)
- United States Army Medical Research Acquisition Activity (W81XWH-10-2-0161)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- mycobacteria, cellular heterogeneity, asymmetric cell division, elongation rate, cell size, antibiotic susceptibility, clonal populations, cell cycle, population heterogeneity
- MeSH terms
- Meropenem, Anti-Bacterial Agents, Cell Cycle, Cell Division, Cell Wall, Cycloserine, Escherichia coli, Isoniazid, Microbial Sensitivity Tests, Mycobacterium tuberculosis, Rifampin, Thienamycins, Time Factors, Mycobacterium smegmatis, Microfluidic Analytical Techniques
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