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Science ; 335(6064): 100-4, 2012 Jan 06.
Article in English | MEDLINE | ID: mdl-22174129

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Mycobacterium smegmatis/drug effects , Mycobacterium smegmatis/growth & development , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Cell Cycle , Cell Division , Cell Wall/metabolism , Cycloserine/pharmacology , Escherichia coli/cytology , Escherichia coli/growth & development , Isoniazid/pharmacology , Meropenem , Microbial Sensitivity Tests , Microfluidic Analytical Techniques , Mycobacterium smegmatis/cytology , Mycobacterium smegmatis/metabolism , Mycobacterium tuberculosis/cytology , Mycobacterium tuberculosis/metabolism , Rifampin/pharmacology , Thienamycins/pharmacology , Time Factors
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