Posttranslational modification of a histone-like protein regulates phenotypic resistance to isoniazid in mycobacteria.
Alexandra SakatosGregory H BabunovicMichael R ChaseAlexander DillsJohn LeszykTracy R RosebrockBryan BrysonSarah M FortunePublished in: Science advances (2018)
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 of the drug-resistant subpopulations of cells, providing the first evidence in prokaryotes that posttranslational modification of a bacterial nucleoid-associated protein may epigenetically regulate cell state.
Keyphrases
- drug resistant
- single cell
- multidrug resistant
- acinetobacter baumannii
- high throughput
- induced apoptosis
- mycobacterium tuberculosis
- dna methylation
- rna seq
- genome wide
- gene expression
- high resolution
- transcription factor
- cell therapy
- cell death
- pseudomonas aeruginosa
- mesenchymal stem cells
- smoking cessation
- mass spectrometry
- heat stress
- heat shock