{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:48:27Z","timestamp":1789519707090,"version":"build-2803163510"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370188"],"award-info":[{"award-number":["32370188"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangzhou Basic and Applied Basic Research Foundation","award":["2025A04J5440"],"award-info":[{"award-number":["2025A04J5440"]}]},{"DOI":"10.13039\/100016691","name":"Guangdong Provincial Pearl River Talents Program","doi-asserted-by":"publisher","award":["2023QN10N029"],"award-info":[{"award-number":["2023QN10N029"]}],"id":[{"id":"10.13039\/100016691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Misuse and overuse of antibiotics have led to the rapid emergence of antibiotic-resistant superbugs. In addition, evidence is emerging that antibiotic exposure could impose substantial influence on bacterial virulence, but the underlying mechanisms remain poorly understood. Here, we discovered a highly conserved aminoglycoside-responsive regulator, AmgR, that inversely modulates the production of destructive toxins [pyocyanin (PYO) and protease] and the inter-bacterial competition weapon [type VI secretion system (H1-T6SS)], which are the signature virulence factors involved in acute and chronic infections, respectively, in Pseudomonas aeruginosa. We demonstrated that AmgR positively regulates PYO and protease productions by directly activating the transcription of their biosynthetic genes and negatively regulates H1-T6SS indirectly through the quorum sensing regulator PqsR. Importantly, we showed that AmgR can be induced by sub-inhibitory concentrations of aminoglycoside antibiotics to trigger the bacterial chronic-to-acute virulence switch, by promoting P.aeruginosa to withdraw from production of the chronic infection-associated virulence factor H1-T6SS to gear up for generation of acute infection related toxins PYO and protease. This study highlights the risks of improper antibiotic usage not only in elevating antibiotic resistance but also in reprogramming bacterial virulence to exacerbate disease dissemination and acute lethality, providing critical insights for the optimization of antibiotic therapies.<\/jats:p>","DOI":"10.1093\/nar\/gkaf471","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T13:00:39Z","timestamp":1749042039000},"source":"Crossref","is-referenced-by-count":5,"title":["An antibiotic-responsive regulator orchestrates chronic-to-acute virulence switch in <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1093","volume":"53","author":[{"given":"Xinbo","family":"Wang","sequence":"first","affiliation":[{"name":"Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, College of Plant Protection,\u00a0South China Agricultural University , Guangzhou ,\u00a0510642,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guizhen","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, College of Plant Protection,\u00a0South China Agricultural University , Guangzhou ,\u00a0510642,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzheng","family":"Zou","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, College of Plant Protection,\u00a0South China Agricultural University , Guangzhou ,\u00a0510642,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiluo","family":"Cao","sequence":"additional","affiliation":[{"name":"Li Ka Shing Faculty of Medicine, The University of Hong Kong Department of Microbiology, , Hong Kong SAR,\u00a0999077,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisheng","family":"Liao","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, College of Plant Protection,\u00a0South China Agricultural University , Guangzhou ,\u00a0510642,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, College of Plant Protection,\u00a0South China Agricultural University , Guangzhou ,\u00a0510642,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5028-2515","authenticated-orcid":false,"given":"Lian-Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, College of Plant Protection,\u00a0South China Agricultural University , Guangzhou ,\u00a0510642,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4662-8111","authenticated-orcid":false,"given":"Zeling","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, College of Plant Protection,\u00a0South China Agricultural University , Guangzhou ,\u00a0510642,\u00a0","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"2025061005174520200_B1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41392-022-01056-1","article-title":"Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics","volume":"7","author":"Qin","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"2025061005174520200_B2","doi-asserted-by":"publisher","first-page":"e14487","DOI":"10.1111\/1751-7915.14487","article-title":"Antibiotic influx and efflux in Pseudomonas aeruginosa: regulation and therapeutic implications","volume":"17","author":"Wu","year":"2024","journal-title":"Microb Biotechnol"},{"key":"2025061005174520200_B3","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1016\/j.gendis.2022.09.009","article-title":"The 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