{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:00:56Z","timestamp":1790744456364,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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. Cell. Infect. Microbiol."],"abstract":"\n Objectives<\/jats:title>\n \n Zinc is widely present in the oral microenvironment and can influence the growth of oral bacteria. ZccR is a MerR-type transcriptional regulator that controls zinc efflux in\n Streptococcus mutans<\/jats:italic>\n (\n S. mutans<\/jats:italic>\n ), but its role in biofilm virulence and interspecies competition with oral commensals remains unclear. This study aimed to investigate the role of ZccR in the formation of single-species biofilms of\n S. mutans<\/jats:italic>\n and dual-species biofilms with oral commensal streptococci, and its underlying regulatory mechanisms.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We constructed an in-frame\n zccR<\/jats:italic>\n knockout mutant of\n S. mutans<\/jats:italic>\n . The growth curve, crystal violet staining, anthrone method, scanning electron microscopy, fluorescence\n in situ<\/jats:italic>\n hybridization, and deferred antagonism assay were used to assess growth, biofilm development, dual-species biofilm composition, and interspecies competitive capacity. RNA-seq was employed to identify genome-wide transcriptional alterations, and promoter-\n lacZ<\/jats:italic>\n reporter strains were constructed to confirm the transcriptional regulation mode of ZccR on\n zccE<\/jats:italic>\n and on itself.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The deletion of\n zccR<\/jats:italic>\n significantly suppressed biofilm formation and water-insoluble exopolysaccharide production of\n S. mutans<\/jats:italic>\n at 150 \u03bcM Zn\n 2+<\/jats:sup>\n , a concentration that only modestly affected planktonic growth. In dual-species biofilms containing\n Streptococcus gordonii (S. gordonii)<\/jats:italic>\n , the mutant exhibited reduced oxidative stress tolerance and weaker inhibition of\n S. gordonii<\/jats:italic>\n , despite upregulation of bacteriocin genes. RNA-sequencing identified 89 differentially expressed genes (67 upregulated and 22 downregulated), including downregulation of the mutanobactin cluster and FAD-dependent oxidoreductases, upregulation of iron-uptake genes, induction of HomR\u2013\n tcy<\/jats:italic>\n -linked cystine-uptake pathways, glutamine biosynthesis, and CRISPR-Cas genes, and a shift from sucrose import (\n scrA\/msmX<\/jats:italic>\n ) toward\n lac<\/jats:italic>\n -dependent lactose\/galactose metabolism. Most of these shifts tracked intracellular zinc accumulation rather than direct ZccR control. Promoter-\n lacZ<\/jats:italic>\n assays revealed that ZccR activates\n zccE<\/jats:italic>\n and represses its own promoter, and zinc acts on these promoters through ZccR-dependent and ZccR-independent routes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n ZccR links zinc homeostasis with biofilm formation and oral interspecies ecology of\n S. mutans<\/jats:italic>\n , thus offering a future intervention point for cariogenic biofilm control.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1946820","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:48:48Z","timestamp":1790743728000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["MerR-type regulator ZccR links zinc homeostasis to biofilm formation and interspecies competition in Streptococcus mutans"],"prefix":"10.3389","volume":"16","author":[{"given":"Yangyang","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaonan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muxin","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyun","family":"Dong","sequence":"additional","affiliation":[{"name":"Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqin","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keke","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/femsle\/fnaf100","article-title":"Transcriptomic response in planktonic and biofilm-associated cells of Streptococcus mutans treated with sublethal concentrations of chlorhexidine","volume":"372","author":"Arbulu","year":"2025","journal-title":"FEMS Microbiol. 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