{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:28:45Z","timestamp":1785364125315,"version":"3.55.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Brucella species (\n                    <jats:italic>Brucella<\/jats:italic>\n                    spp.) are facultative intracellular zoonotic pathogens responsible for brucellosis, a disease causing substantial global public health and economic burdens. Rifampicin remains a first-line therapeutic agent, but the molecular mechanisms underlying rifampicin resistance in\n                    <jats:italic>Brucella<\/jats:italic>\n                    remain poorly defined, especially the contribution of ribosome-associated regulatory proteins. HflX is a conserved ribosome-binding GTPase involved in ribosomal quality control and antibiotic resistance, yet its role in rifampicin resistance has not been reported. Here, we constructed\n                    <jats:italic>hflX<\/jats:italic>\n                    deletion and complemented strains of\n                    <jats:italic>Brucella<\/jats:italic>\n                    abortus 2308 and characterized their phenotypes using antimicrobial susceptibility tests, growth and time-kill assays, electron microscopy, proteomics, and RT-qPCR. Deletion of\n                    <jats:italic>hflX<\/jats:italic>\n                    significantly increased bacterial susceptibility to rifampicin, impaired growth recovery, and intensified intracellular stress without disrupting cell envelope integrity. Mechanistically,\n                    <jats:italic>hflX<\/jats:italic>\n                    depletion led to coordinated downregulation of RNA polymerase (RNAP) core subunits (\n                    <jats:italic>rpoA<\/jats:italic>\n                    ,\n                    <jats:italic>rpoB<\/jats:italic>\n                    , and\n                    <jats:italic>rpoC<\/jats:italic>\n                    ) and \u03c3 factors (\n                    <jats:italic>rpoD<\/jats:italic>\n                    and\n                    <jats:italic>rpoH<\/jats:italic>\n                    ) at both protein and mRNA levels. Our findings demonstrate that HflX mediates rifampicin resistance in\n                    <jats:italic>Brucella<\/jats:italic>\n                    by regulating RNAP-associated gene expression and metabolic adaptation, establishing a novel HflX\u2013RNAP regulatory axis. This study expands the understanding of antibiotic resistance in intracellular pathogens and highlights HflX as a promising target for developing anti-resistance strategies against brucellosis.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1823866","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:41:59Z","timestamp":1776231719000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["HflX mediates rifampicin resistance in Brucella by downregulating the expression of RNA polymerase-associated genes"],"prefix":"10.3389","volume":"17","author":[{"given":"Hao","family":"Geng","sequence":"first","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Veterinary Medicine, Lanzhou University","place":["Lanzhou, China"]},{"name":"Gansu Province Research Center for Basic Disciplines of Pathogen Biology","place":["Lanzhou, China"]},{"name":"Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhu","family":"Qi","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Veterinary Medicine, Lanzhou University","place":["Lanzhou, China"]},{"name":"Gansu Province Research Center for Basic Disciplines of Pathogen Biology","place":["Lanzhou, China"]},{"name":"Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengru","family":"Su","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Veterinary Medicine, Lanzhou University","place":["Lanzhou, China"]},{"name":"Gansu Province Research Center for Basic Disciplines of Pathogen Biology","place":["Lanzhou, China"]},{"name":"Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feijie","family":"Zhi","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Veterinary Medicine, Lanzhou University","place":["Lanzhou, China"]},{"name":"Gansu Province Research Center for Basic Disciplines of Pathogen Biology","place":["Lanzhou, China"]},{"name":"Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefeng","family":"Chu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, College of Veterinary Medicine, Lanzhou University","place":["Lanzhou, China"]},{"name":"Gansu Province Research Center for Basic Disciplines of Pathogen Biology","place":["Lanzhou, China"]},{"name":"Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.chom.2024.05.015","article-title":"Antibiotic resistance: A key microbial survival mechanism that threatens public health.","volume":"32","author":"Abbas","year":"2024","journal-title":"Cell Host Microbe"},{"key":"B2","doi-asserted-by":"publisher","first-page":"167330","DOI":"10.1016\/j.jmb.2021.167330","article-title":"NusG-mediated coupling of transcription and translation enhances gene expression by suppressing RNA polymerase backtracking.","volume":"434","author":"Bailey","year":"2022","journal-title":"J. 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