{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:20:30Z","timestamp":1793132430446,"version":"4.5.0"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"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:sec><jats:title>Introduction<\/jats:title><jats:p>Response regulators from diverse two-component systems often function as diguanylate cyclases or phosphodiesterases, thereby enabling precise regulation of intracellular c-di-GMP levels to control bacterial virulence and motility. However, the regulatory mechanisms of c-di-GMP require further elucidation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study confirmed that ArrS and ArrR form a two-component system via structural analysis, two-hybrid, and phosphodiesterase activity detection. To evaluate the impact of ArrS\/ArrR on intracellular c-di-GMP levels, biofilm detection, motility detection, fluorescence reporter plasmids, and LC-MS\/MS analysis were employed. One-hybrid, EMSA, and RT-qPCR were used to demonstrate the function of ArgR on arrSR promoter. The roles of ArrS\/ArrR in <jats:italic>Aeromonas veronii<\/jats:italic> were investigated using RT-qPCR, murine model, and proteomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ArrS and ArrR constituted a two-component system in <jats:italic>Aeromonas veronii<\/jats:italic> and were transcriptionally repressed by ArgR. ArrR exhibited phosphodiesterase activity, which is inhibited through phosphorylation mediated by ArrS. In <jats:italic>Aeromonas veronii<\/jats:italic>, ArrS\/ArrR significantly altered the intracellular c-di-GMP levels. In a murine model, \u0394<jats:italic>arrS<\/jats:italic> exhibited increased pathogenicity, leading to elevated TNF-\u03b1 and IFN-\u03b3 levels in serum, and severer toxicity to spleen and kidney. These effects might be elucidated by the upregulated inflammation-associated proteins in \u0394<jats:italic>arrS<\/jats:italic>. Moreover, the exonuclease RecB was also up-regulated in \u0394<jats:italic>arrS<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We elucidated the regulatory mechanism of ArrS\/ArrR on intracellular c-di-GMP levels and its impact on the virulence in <jats:italic>Aeromonas veronii<\/jats:italic>, and discussed the intricate relationship between c-di-GMP metabolism and arginine metabolism.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1527317","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T16:01:33Z","timestamp":1738252893000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel two-component system contributing the catabolism of c-di-GMP influences virulence in Aeromonas veronii"],"prefix":"10.3389","volume":"16","author":[{"given":"Chaolun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1681\/ASN.2015111285","article-title":"Intestinal dysbiosis, barrier dysfunction, and bacterial translocation account for CKD-related systemic inflammation","volume":"28","author":"Andersen","year":"2017","journal-title":"J. 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