{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T15:39:10Z","timestamp":1787931550184,"version":"build-2784847793"},"reference-count":38,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32100020, 32370188"],"award-info":[{"award-number":["32100020, 32370188"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2023A1515012775, 2022A1515010194"],"award-info":[{"award-number":["2023A1515012775, 2022A1515010194"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Guangzhou Basic and Applied Basic Research Foundation","award":["202201010613"],"award-info":[{"award-number":["202201010613"]}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"crossref","award":["19201901"],"award-info":[{"award-number":["19201901"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Zinc is an important transition metal that is essential for numerous physiological processes while excessive zinc is cytotoxic.\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              is a ubiquitous opportunistic human pathogen equipped with an exquisite zinc homeostatic system, and the two-component system CzcS\/CzcR plays a key role in zinc detoxification. Although an increasing number of studies have shown the versatility of CzcS\/CzcR, its physiological functions are still not fully understood. In this study, transcriptome analysis was performed, which revealed that CzcS\/CzcR is silenced in the absence of the zinc signal but modulates global gene expression when the pathogen encounters zinc excess. CzcR was demonstrated to positively regulate the copper tolerance gene\n              <jats:italic>ptrA<\/jats:italic>\n              and negatively regulate the pyochelin biosynthesis regulatory gene\n              <jats:italic>pchR<\/jats:italic>\n              through direct binding to their promoters. Remarkably, the upregulation of\n              <jats:italic>ptrA<\/jats:italic>\n              and downregulation of\n              <jats:italic>pchR<\/jats:italic>\n              were shown to rescue the impaired capacity of copper tolerance and prevent pyochelin overproduction, respectively, caused by zinc excess. This study not only advances our understanding of the regulatory spectrum of CzcS\/CzcR but also provides new insights into stress adaptation mediated by two-component systems in bacteria to balance the cellular processes that are disturbed by their signals.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              CzcS\/CzcR is a two-component system that has been found to modulate zinc homeostasis, quorum sensing, and antibiotic resistance in\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              . To fully understand the physiological functions of CzcS\/CzcR, we performed a comparative transcriptome analysis in this study and discovered that CzcS\/CzcR controls global gene expression when it is activated during zinc excess. In particular, we demonstrated that CzcS\/CzcR is critical for maintaining copper tolerance and iron homeostasis, which are disrupted during zinc excess, by inducing the expression of the copper tolerance gene\n              <jats:italic>ptrA<\/jats:italic>\n              and repressing the pyochelin biosynthesis genes through\n              <jats:italic>pchR<\/jats:italic>\n              . This study revealed the global regulatory functions of CzcS\/CzcR and described a new and intricate adaptive mechanism in response to zinc excess in\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              . The findings of this study have important implications for novel anti-infective interventions by incorporating metal-based drugs.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aem.02327-23","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T14:13:11Z","timestamp":1708438391000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Activation of CzcS\/CzcR during zinc excess regulates copper tolerance and pyochelin biosynthesis of\n            <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","author":[{"given":"Ting","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou, 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