Antibiotic treatment and selection for <i>glpK</i> mutations in patients with active tuberculosis disease

We read with great interest the paper by Safi et al. (1) describing frameshifts in glpK ’s homopolymeric tract (HT) of seven cytosines (7C) as a potential cause of antibiotic tolerance. These results have implications for tuberculosis (TB) treatment, but other forces than antibiotic pressure may be responsible for the emergence of glpK mutations (1, 2). We raise the possibilities of selection in vitro, selection in vivo from nonantibiotic host factors, and population bottlenecks in determining the fate of glpK frameshifts. In a recent study (3), we observed the landscape of Mycobacterium tuberculosis mutations occurring longitudinally in-host for 200 subjects with active TB disease. We tracked mutations arising in-host between two sputum samples taken at different time points during and/or after treatment. To … [↵][1]1To whom correspondence may be addressed. Email: roger_vargas{at}g.harvard.edu. [1]: #xref-corresp-1-1