title: Asymmetry and aging of mycobacterial cells lead to variable growth and antibiotic susceptibility.
abstract: Cells use both deterministic and stochastic mechanisms to generate cell-to-cell heterogeneity, which enables the population to better withstand environmental stress. Here we show that, within a clonal population of mycobacteria, there is deterministic heterogeneity in elongation rate that arises because mycobacteria grow in an unusual, unipolar fashion. Division of the asymmetrically growing mother cell gives rise to daughter cells that differ in elongation rate and size. Because the mycobacterial cell division cycle is governed by time, not cell size, rapidly elongating cells do not divide more frequently than slowly elongating cells. The physiologically distinct subpopulations of cells that arise through asymmetric growth and division are differentially susceptible to clinically important classes of antibiotics.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Bree B
authors.initials: BB
authors.lastname: Aldridge
authors.forename: Marta
authors.initials: M
authors.lastname: Fernandez-Suarez
authors.forename: Danielle
authors.initials: D
authors.lastname: Heller
authors.forename: Vijay
authors.initials: V
authors.lastname: Ambravaneswaran
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
authors.forename: Mehmet
authors.initials: M
authors.lastname: Toner
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Fortune
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002453:Cell Cycle; D002455:Cell Division; D002473:Cell Wall / Q000378:metabolism; D003523:Cycloserine / Q000494:pharmacology; D004926:Escherichia coli / Q000166:cytology / Q000254:growth & development; D007538:Isoniazid / Q000494:pharmacology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D046210:Microfluidic Analytical Techniques; D020102:Mycobacterium smegmatis / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology; D013845:Thienamycins / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D003523:Cycloserine; D000077731:Meropenem; D007538:Isoniazid; D012293:Rifampin