Posttranslational modification of a histone-like protein regulates phenotypic resistance to isoniazid in mycobacteria.

ABSTRACT: There is increasing evidence that phenotypically drug-resistant bacteria may be important determinants of antibiotic treatment failure. Using high-throughput imaging, we defined distinct subpopulations of mycobacterial cells that exhibit heritable but semi-stable drug resistance. These subpopulations have distinct transcriptional signatures and growth characteristics at both bulk and single-cell levels, which are also heritable and semi-stable. We find that the mycobacterial histone-like protein HupB is required for the formation of these subpopulations. Using proteomic approaches, we further demonstrate that HupB is posttranslationally modified by lysine acetylation and lysine methylation. Mutation of a single posttranslational modification site specifically abolishes the formation of one

SUBMITTER: Sakatos A 

PROVIDER: S-EPMC5931751 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature