Cited by 454Bacterial Genetics and BiotechnologyTuberculosis Research and EpidemiologyGene Regulatory Network Analysis

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Asymmetry and Aging of Mycobacterial Cells Lead to Variable Growth and Antibiotic Susceptibility

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Aldridge, Bree B., Fernandez-Suarez, Marta, Heller, Danielle, Ambravaneswaran, Vijay, Irimia, Daniel, Toner, Mehmet, Fortune, Sarah M.·2012·Science

DOI 10.1126/science.1216166PMC PMC3397429

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Abstract

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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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.
ORCID: Aldridge, Bree B.
Heller, Danielle
Irimia, Daniel
Toner, Mehmet
Fortune, Sarah M.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2012-01-06
Volume: 335
Issue: 6064
Pages: 100-104
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1216166
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
Licence: www.sciencemag.org/site/feature/contribinfo/prep/license.xhtml (vor)
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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Asymmetry and Aging of Mycobacterial Cells Lead to Variable Growth and Antibiotic Susceptibility

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