Posttranslational Modification of a Histone-like Protein Regulates Phenotypic Resistance to Isoniazid in Mycobacteria

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2018 May 8

PMID 29732401

Citations 40

Authors

Alexandra Sakatos

Gregory H Babunovic

Michael R Chase

Alexander Dills

John Leszyk

Tracy Rosebrock

Bryan Bryson

Sarah M Fortune

Affiliations

Soon will be listed here.

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 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.

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