Posttranslational modification of a histone-like protein regulates phenotypic resistance to isoniazid in mycobacteria
dc.contributor.author | Sakatos, Alexandra | |
dc.contributor.author | Babunovic, Gregory H. | |
dc.contributor.author | Chase, Michael R. | |
dc.contributor.author | Dills, Alexander | |
dc.contributor.author | Leszyk, John D. | |
dc.contributor.author | Rosebrock, Tracy | |
dc.contributor.author | Bryson, Bryan | |
dc.contributor.author | Fortune, Sarah M. | |
dc.date | 2022-08-11T08:09:50.000 | |
dc.date.accessioned | 2022-08-23T16:45:24Z | |
dc.date.available | 2022-08-23T16:45:24Z | |
dc.date.issued | 2018-05-02 | |
dc.date.submitted | 2018-07-06 | |
dc.identifier.citation | <p>Sci Adv. 2018 May 2;4(5):eaao1478. doi: 10.1126/sciadv.aao1478. eCollection 2018 May.. <a href="https://doi.org/10.1126/sciadv.aao1478">Link to article on publisher's site</a></p> | |
dc.identifier.issn | 2375-2548 (Linking) | |
dc.identifier.doi | 10.1126/sciadv.aao1478 | |
dc.identifier.pmid | 29732401 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/40673 | |
dc.description.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. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=29732401&dopt=Abstract">Link to Article in PubMed</a></p> | |
dc.rights | Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | |
dc.subject | Amino Acids, Peptides, and Proteins | |
dc.subject | Biochemistry, Biophysics, and Structural Biology | |
dc.subject | Microbiology | |
dc.title | Posttranslational modification of a histone-like protein regulates phenotypic resistance to isoniazid in mycobacteria | |
dc.type | Journal Article | |
dc.source.journaltitle | Science advances | |
dc.source.volume | 4 | |
dc.source.issue | 5 | |
dc.identifier.legacyfulltext | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4485&context=oapubs&unstamped=1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/oapubs/3474 | |
dc.identifier.contextkey | 12450255 | |
refterms.dateFOA | 2022-08-23T16:45:24Z | |
html.description.abstract | <p>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.</p> | |
dc.identifier.submissionpath | oapubs/3474 | |
dc.contributor.department | Department of Biochemistry and Molecular Pharmacology | |
dc.source.pages | eaao1478 |