Antimicrobial photodynamic therapy (aPDT) with curcumin controls intradermal infection by Staphylococcus aureus in mice with type 1 diabetes mellitus: a pilot study.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main pathogens that cause infections in diabetic individuals. In this paper, we report the outcomes of our investigation on the intradermal application of antimicrobial photodynamic therapy (PDT) with curcumin in an infection induced by MRSA ATCC 43300 strain in the ear of mice with Type 1 Diabetes Mellitus (T1DM). A solution containing 100 µg of curcumin was photoactivated ex vivo with a LED light (450 nm) delivering a fluency of 13.5 J/cm3. This solution was administered in the ear intradermally, at the same inoculum site as the MRSA ATCC 43300 strain (PDT Group). This study also included the use of two control groups (both infected): One was treated with saline and the other was treated with non-photoactivated curcumin. The animals were euthanized 24 h after these treatments and samples of draining lymph node and treated ear were collected for examination. The PDT group showed lower bacterial load in the draining lymph node when compared to the saline and curcumin groups (p-value <0.05) 24 h after treatment. In addition to bacterial load, the PDT group presented a higher concentration of nitrates and nitrites in the draining lymph node when compared to the saline and curcumin groups (p-value <0.001). Examining the infectious site, despite apparently having similar inflammatory cell recruitment compared with the control groups, the PDT group showed a profile with less intense activity in the myeloperoxidase expression when compared to the saline group (p-value <0.001). Additionally, the detected concentration of cytokines such as IL-1ß, IL-12, and IL-10 was significantly lower in the PDT group when compared to the saline group (p-value <0.01; p-value <0.05; p-value <0.05, respectively), thus presenting a less intense inflammatory response during infection resolution. Our pilot study showed for the first time the therapeutic potential of PDT using curcumin when administered intradermally in the treatment of infections caused by S. aureus in mice with T1DM.

Anticariogenic activities of Libidibia ferrea, gallic acid and ethyl gallate against Streptococcus mutans in biofilm model.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, ethnopharmacological studies show that Libidibia ferrea (Mart. ex Tul.) L. P. Queiroz is commonly used in folk medicine as an antifungal, antimicrobial and anti-inflammatory. In the Amazon region, the dried fruit powder of L. ferrea are widely used empirically by the population in an alcoholic tincture as an antimicrobial mouthwash in oral infections and the infusion is also recommended for healing oral wounds. However, there are few articles that have evaluated the antimicrobial activity against oral pathogens in a biofilm model, identifying active compounds and mechanisms of action. AIM OF THE STUDY: The aim of this study was to evaluate the antimicrobial and anti-adherence activities of the ethanolic extract, fractions and isolated compounds (gallic acid and ethyl gallate) of the fruit and seed of L. ferrea against Streptococcus mutans. The inhibition of acidicity/acidogenicity and the expression of the S. mutans GTF genes in biofilms were also evaluated. MATERIALS AND METHODS: Minimal Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Minimum Inhibitory Concentration of Cell Adhesion (MICA) were evaluated with ethanolic extract (EELF), fractions, gallic acid (GA) and ethyl gallate (EG) against S. mutans. Inhibition of biofilm formation, pH drop and proton permeability tests were conducted with EELF, GA and EG, and also evaluated the expression of the GTF genes in biofilms. The compounds of dichloromethane fraction were identified by GC-MS. RESULTS: This is the first report of shikimic, pyroglutamic, malic and protocatechuic acids identified in L. ferrea. EELF, GA and EG showed MIC at 250 µg/mL, and MBC at 1000 µg/mL by EELF. EELF biofilms showed reduced dry weight and acidogenicity of S. mutans in biofilms. GA and EG reduced viable cells, glucans soluble in alkali, acidogenicity, aciduricity and downregulated expression of gtfB, gtfC and gtfD genes in biofilms. SEM images of GA and EG biofilms showed a reduction of biomass, exopolysaccharide and microcolonies of S. mutans. CONCLUSIONS: The ethanolic extract of fruit and seed of L. ferrea, gallic acid and ethyl gallate showed great antimicrobial activity and inhibition of adhesion, reduction of acidogenicity and aciduricity in S. mutans biofilms. The results obtained in vitro validate the use of this plant in ethnopharmacology, and open opportunities for the development of new oral anticariogenic agents, originated by plants that can inhibit pathogenic biofilm that leads to the development of caries.