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Major virulence factors that are associated with the cariogenicity of <jats:italic>S. mutans<\/jats:italic> include adhesion, acidogenicity and acidurity. All these pathogenic traits coordinate and alter the dental plaque ecology which provide room for interaction with other similar acidogenic and aciduric bacteria. This cariogenic flora increases the possibility of enamel demineralization which headway to caries development. The present study was aimed at evaluating the antimicrobial and antiinfective potential of a lichen secondary metabolite usnic acid (UA) against <jats:italic>S. mutans.<\/jats:italic> Minimum inhibitory concentration (MIC), Minimum bactericidal concentration (MBC) and growth kinetics were evaluated to determine the antimicrobial potential of UA against <jats:italic>S. mutans.<\/jats:italic> UA at 5\u00a0\u00b5g\u00a0mL<jats:sup>\u22121<\/jats:sup> and 10\u00a0\u00b5g\u00a0mL<jats:sup>\u22121<\/jats:sup> concentration were considered as MIC and MBC respectively. Effect on biofilm formation was microscopically assessed and found to be reduced in a concentration dependent manner. Gene expression of <jats:italic>gtfB, gtfC, gtfD, vicR, ComDE<\/jats:italic> and <jats:italic>smu0630<\/jats:italic> was found to be downregulated upon treatment with sub-MIC of UA. Acidogenicity, acidurity, eDNA synthesis and response to oxidative stress were found to be attenuated by the influence of UA. It was also demonstrated to act on preformed mature biofilm of <jats:italic>S. mutans.<\/jats:italic> Moreover, UA was shown to possess very low frequency to acquire spontaneous resistance development in <jats:italic>S. mutans.<\/jats:italic> Besides, no morphological aberrations or toxic effect was instigated by UA in the human buccal epithelial cells as well as to the oral commensals. Altogether, these results demonstrate the therapeutic potential of usnic acid in the treatment of <jats:italic>S. mutans<\/jats:italic> infection.<\/jats:p>","DOI":"10.1038\/s41598-020-80338-6","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T11:11:08Z","timestamp":1610622668000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Usnic acid deteriorates acidogenicity, acidurance and glucose metabolism of Streptococcus mutans through downregulation of two-component signal transduction systems"],"prefix":"10.1038","volume":"11","author":[{"given":"Arumugam","family":"Priya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra Bose Manish","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaguvel","family":"Valliammai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthonymuthu","family":"Selvaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunmugiah Karutha","family":"Pandian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"80338_CR1","doi-asserted-by":"publisher","first-page":"e13135","DOI":"10.1371\/journal.pone.0013135","volume":"5","author":"K Standar","year":"2010","unstructured":"Standar, K. et al. 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