Ursolic acid inhibits multi-species biofilms developed by Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii. 2021

Xiaoying Lyu, and Liang Wang, and Yusen Shui, and Qingsong Jiang, and Lan Chen, and Wen Yang, and Xiaoya He, and Jumei Zeng, and Yuqing Li
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.

OBJECTIVE The current study aimed to assess the antimicrobial activity of ursolic acid (UA) against multi-species biofilms formed by Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii, as well as to measure its biocompatibility. METHODS Crystal violet staining, CFU counting, CCK-8 assays and scanning electron microscopy (SEM) were applied to investigate the effect of UA on multi-species biofilms. UA's effect on exopolysaccharides (EPS) production was measured using confocal laser scanning microscopy (CLSM) and the anthrone-sulfuric acid method. Fluorescent in situ hybridization (FISH) was applied to visualize and quantify the microbial composition of multi-species biofilms. Quantitative real-time PCR (qRT-PCR) was used to measure the expression of virulence genes of S. mutans, S. sanguinis, and S. gordonii under UA treatment. Moreover, CCK-8 assays were performed to evaluate its cytotoxicity against human oral keratinocytes (HOKs) and human gingival epithelial cells (HGEs). RESULTS The results showed that UA had significant antimicrobial activity against common oral streptococci. UA also reduced the EPS synthesis of oral streptococci and suppressed gtf genes' expression. In addition, UA reduced the proportion of S. mutans in multi-species biofilms. Besides, UA had low cytotoxicity against HOKs and HGEs. CONCLUSIONS UA exhibited antibiofilm activity against oral pathogenic bacteria and had the potential to be used in dental caries treatment.

UI MeSH Term Description Entries
D003731 Dental Caries Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. Caries, Dental,Carious Lesions,Dental Cavities,Dental Cavity,Dental Decay,Dental White Spots,Carious Dentin,Decay, Dental,Dental White Spot,White Spot, Dental,White Spots, Dental,Carious Dentins,Carious Lesion,Cavities, Dental,Cavity, Dental,Dentin, Carious,Dentins, Carious,Lesion, Carious,Lesions, Carious,Spot, Dental White,Spots, Dental White
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000097245 Ursolic Acid A pentacyclic triterpene that co-occurs with its isomer OLEANOLIC ACID in several plant species, and occurs in large amounts in FRUITS (such as CRANBERRIES; PEARS; PLUMS; and OLIVES), MEDICINAL HERBS, and other plants. (+)-Ursolic Acid,(3 beta)-3-Hydroxyurs-12-en-28-oic Acid,3-Epi-Ursolic Acid,3-Epiursolic Acid,3alpha-Ursolic Acid,3beta-Ursolic Acid,Olean-12-en-28-oic Acid, 3-Hydroxy-, Sodium Salt (1:1), (3beta)-,Sodium Oleanolate,Ursolic Acid Monosodium Salt,Ursolic Acid Sodium Salt,Ursolic Acid, (3beta)-Isomer, 2-(14)C-Labeled,Ursolic Acid, (3beta)-Isomer, Monopotassium Salt,Merotaine,3 Epi Ursolic Acid,3 Epiursolic Acid,3alpha Ursolic Acid,3beta Ursolic Acid,Oleanolate, Sodium
D013295 Streptococcus mutans A polysaccharide-producing species of STREPTOCOCCUS isolated from human dental plaque.
D013298 Streptococcus sanguis A gram-positive organism found in dental plaque, in blood, on heart valves in subacute endocarditis, and infrequently in saliva and throat specimens. L-forms are associated with recurrent aphthous stomatitis. Streptococcus sanguinis
D014315 Triterpenes A class of terpenes (the general formula C30H48) formed by the condensation of six isoprene units, equivalent to three terpene units. Triterpene,Triterpenoid,Triterpenoids
D017404 In Situ Hybridization, Fluorescence A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. FISH Technique,Fluorescent in Situ Hybridization,Hybridization in Situ, Fluorescence,FISH Technic,Hybridization in Situ, Fluorescent,In Situ Hybridization, Fluorescent,FISH Technics,FISH Techniques,Technic, FISH,Technics, FISH,Technique, FISH,Techniques, FISH
D054773 Streptococcus gordonii A species of gram-positive, facultatively anaerobic bacteria in the family STREPTOCOCCACEAE. It is a normal inhabitant of the human oral cavity, and causes DENTAL PLAQUE and ENDOCARDITIS. It is being investigated as a vehicle for vaccine delivery.
D018441 Biofilms Encrustations formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedded in an EXTRACELLULAR POLYMERIC SUBSTANCE MATRIX that is secreted by the microbes. They occur on body surfaces such as teeth (DENTAL DEPOSITS); inanimate objects, and bodies of water. Biofilms are prevented from forming by treating surfaces with DENTIFRICES; DISINFECTANTS; ANTI-INFECTIVE AGENTS; and anti-fouling agents. Biofilm

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