Therapeutic Potential of Punica granatum and Isolated Compounds: Evidence-Based Advances to Treat Bacterial Infections.

Punica granatum Linn has been known for its nutritional and medicinal value since ancient times and is used in the treatment of various pathologies owing to its antibacterial properties. This review reports the results of the most recent studies on the antibacterial effects of P. granatum and its isolated compounds on bacteria of clinical interest. A search in the PubMed, Scopus, Science Direct, and Science Citation Index Expanded (Web of Science) databases was performed, which included articles that evaluated the antibacterial activity of P. granatum extracts and excluded articles that analyzed other microorganisms or nonpathogenic bacteria, as well as theses, dissertations, duplicate articles, and those not fully available. The literature suggests that P. granatum extracts can act on bacteria, such as methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In addition, fruit peel was the most commonly used pharmacogen and methanol, ethanol, and water were the most common solvents for the extraction of bioactive compounds. The antibacterial potential of the methanolic extract of pomegranate peel could be attributed to the presence of active compounds, such as 5-hydroxymethylfurfural, punicic acid, gallic acid, and punicalagin. Thus, there is evidence that these plant extracts, having high polyphenol content, can disrupt the bacterial plasma membrane and inhibit the action of proteins related to antimicrobial resistance. P. granatum shows antibacterial activity against Gram-positive and Gram-negative bacteria, with great potential against multidrug-resistant strains. Further research is needed to clarify the mechanism of action related to this biological activity and investigate the isolated substances that may be responsible for the antibacterial effects.

Analysis of the Effect of the TRPC4/TRPC5 Blocker, ML204, in Sucrose-Induced Metabolic Imbalance.

Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in the food industry and found in a range of fast, restaurant, and processed foods. Herein, we investigated the effects of a TRPC4/TRPC5 blocker, ML204, in the metabolic imbalances triggered by early exposure to sucrose-enriched diet in mice. TRPC4 and TRPC5 belong to the family of non-selective Ca+2 channels known as transient receptor potential channels. High-sucrose (HS)-fed animals with hyperglycaemia and dyslipidaemia, were accompanied by increased body mass index. mesenteric adipose tissue accumulation with larger diameter cells and hepatic steatosis in comparison to those fed normal diet. HS mice also exhibited enhanced adipose, liver, and pancreas TNFα and VEGF levels. ML204 exacerbated hyperglycaemia, dyslipidaemia, fat tissue deposition, hepatic steatosis, and adipose tissue and liver TNFα in HS-fed mice. Normal mice treated with the blocker had greater hepatic steatosis and adipose tissue cell numbers/diameter than those receiving vehicle, but showed no significant changes in tissue inflammation, glucose, and lipid levels. The results indicate that TRPC4/TRPC5 protect against the metabolic imbalances caused by HS ingestion.

The Immunomodulatory Activity of Punica granatum L. Peel Extract Increases the Lifespan of Mice with Lethal Sepsis.

Sepsis is an organ dysfunction syndrome associated with high mortality. To date, no effective treatment is available to combat this disease. Punica granatum L. is a potential alternative treatment due to its anti-inflammatory, antimicrobial, and antioxidant properties. Thus, this study aimed to evaluate the effects of a hydroalcoholic crude extract from the peels of P. granatum (HCEPg) in mice with lethal sepsis. Lethal polymicrobial sepsis was induced in female Swiss mice via cecal ligation and puncture (CLP). Initially, the animals were divided into three groups: Sham (false-operated), CLP-control (phosphate-buffered saline), and CLP-HCEPg (single dose, 5 mg/kg, subcutaneous administration). Treatment was initiated immediately after the induction of sepsis, and survival was evaluated every 12 hr for 5 days. Those who survived were euthanized. Serum cytokine levels were measured using a cytometric bead array Mouse Inflammatory Cytokine Kit. The number of colony-forming units, as well as the number of cells in the lymphoid organs and their activation markers, were analyzed. Results showed that treatment with HCEPg increased lifespan and reduced bacterial counts in the peritoneum, bloodstream, and spleen. HCEPg also decreased hydrogen peroxide secretion by phagocytes and augmented serum IL-10 levels, indicating its systemic anti-inflammatory effects. Additionally, treatment with HCEPg attenuated infection-induced lung hemorrhage. Overall, P. granatum extract improved the lifespan of septic mice, possibly due to its antimicrobial, anti-inflammatory, and immunomodulatory effects, thereby regulating bacterial load and translocation, as well as controlling the systemic inflammation induced by sepsis.

Antimicrobial and Anti-Infective Activity of Natural Products-Gaining Knowledge from Novel Studies.

Despite advances in the development of antimicrobial drugs in the last centuries, antimicrobial resistance has consistently raised in the last decades, compromising their effectiveness. Novel antimicrobial compounds, especially from natural sources, including plants, microorganisms, and animals, have since become a growing area of research. In this context, studies covering the investigation of their ability to combat resistant microorganisms, either by neutralization or inactivation of pathogen resistance mechanisms and virulence properties, have gained attention. Herein, a collection of 19 manuscripts focused on the antimicrobial and anti-infective activity of natural products, including their mechanisms of action, in silico evidence of antimicrobial activity, synergistic associations with antibiotics, and other aspects, will be discussed.

Immunomodulatory Activity of Probiotics in Models of Bacterial Infections.

As resistance to conventional antibiotics among bacteria continues to increase, researchers are increasingly focusing on alternative strategies for preventing and treating bacterial infections, one of which is microbiota modulation. The objective of this review is to analyze the scientific literature on the immunomodulatory effects of probiotics in bacterial infections. This is an integrative review of the literature based on systematic steps, with searches performed in the databases Medline, PubMed, Scopus, Embase, and ScienceDirect. The most prevalent bacterial genera used to evaluate infectious processes were Salmonella, Escherichia, Klebsiella, and Streptococcus. Lactobacillus was the most commonly used probiotic genus, with Lactobacillus delbrueckii subsp. bulgaricus is the most frequently used species. In most studies, prophylactic treatment with concentrations of probiotics equal to or greater than 8 log CFU/mL was chosen. However, there was considerable heterogeneity in terms of effective treatment duration, indicating that the results cannot be generalized across all studies. This review found that probiotics interact with the immune system through different mechanisms and have a positive effect on preventing different types of bacterial infections.

In Silico and In Vitro Analysis of Sulforaphane Anti-Candida Activity.

Oropharyngeal candidiasis/candidosis is a common and recurrent opportunistic fungal infection. Fluconazole (FLZ), one of the most used and effective antifungal agents, has been associated with a rise of resistant Candida species in immunocompromised patients undergoing prophylactic therapy. Sulforaphane (SFN), a compound from cruciferous vegetables, is an antimicrobial with yet controversial activities and mechanisms on fungi. Herein, the in silico and antifungal activities of SFN against C. albicans were investigated. In silico analyzes for the prediction of the biological activities and oral bioavailability of SFN, its possible toxicity and pharmacokinetic parameters, as well as the estimates of its gastrointestinal absorption, permeability to the blood-brain barrier and skin, and similarities to drugs, were performed by using different software. SFN in vitro anti-Candida activities alone and in combination with fluconazole (FLZ) were determined by the broth microdilution method and the checkerboard, biofilm and hyphae formation tests. Amongst the identified probable biological activities of SFN, nine indicated an antimicrobial potential. SFN was predicted to be highly absorbable by the gastrointestinal tract, to present good oral availability, and not to be irritant and/or hepatotoxic. SFN presented antifungal activity against C. albicans and prevented both biofilm and hyphae formation by this microorganism. SFN was additive/synergistic to FLZ. Overall, the data highlights the anti-Candida activity of SFN and its potential to be used as an adjuvant therapy to FLZ in clinical settings.

Schinus terebinthifolius Leaf Lectin (SteLL) Reduces the Bacterial and Inflammatory Burden of Wounds Infected by Staphylococcus aureus Promoting Skin Repair.

Staphylococcus aureus is commonly found in wound infections where this pathogen impairs skin repair. The lectin isolated from leaves of Schinus terebinthifolius (named SteLL) has antimicrobial and antivirulence action against S. aureus. This study evaluated the effects of topical administration of SteLL on mice wounds infected by S. aureus. Seventy-two C57/BL6 mice (6−8 weeks old) were allocated into four groups: (i) uninfected wounds; (ii) infected wounds, (iii) infected wounds treated with 32 µg/mL SteLL solution; (iv) infected wounds treated with 64 µg/mL SteLL solution. The excisional wounds (64 mm2) were induced on the dorsum and infected by S. aureus 432170 (4.0 × 106 CFU/wound). The daily treatment started 1-day post-infection (dpi). The topical application of both SteLL concentrations significantly accelerated the healing of S. aureus-infected wounds until the 7th dpi, when compared to untreated infected lesions (reductions of 1.95−4.55-fold and 1.79−2.90-fold for SteLL at 32 µg/mL and 64 µg/mL, respectively). The SteLL-based treatment also amended the severity of wound infection and reduced the bacterial load (12-fold to 72-fold for 32 µg/mL, and 14-fold to 282-fold for 64 µg/mL). SteLL-treated wounds show higher collagen deposition and restoration of skin structure than other groups. The bacterial load and the levels of inflammatory markers (IL-6, MCP-1, TNF-α, and VEGF) were also reduced by both SteLL concentrations. These results corroborate the reported anti-infective properties of SteLL, making this lectin a lead candidate for developing alternative agents for the treatment of S. aureus-infected skin lesions.

Ethyl Acetate Fraction of Bixa orellana and Its Component Ellagic Acid Exert Antibacterial and Anti-Inflammatory Properties against Mycobacterium abscessus subsp. massiliense.

Mycobacterium abscessus subsp. massiliense (Mabs) causes chronic infections, which has led to the need for new antimycobacterial agents. In this study, we investigated the antimycobacterial and anti-inflammatory activities of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc). In silico analysis predicted that ElAc had low toxicity, was not mutagenic or carcinogenic, and had antimicrobial and anti-inflammatory activities. Apparently, ElAc can interact with COX2 and Dihydrofolate reductase (DHFR) enzymes, which could explain both activities. In vitro analysis showed that BoEA and ElAc exerted antimicrobial activity against Mabs (minimum inhibitory concentration of 1.56, 1.56 mg/mL and bactericidal concentration of 6.25, 3.12 mg/mL, respectively. Clarithromycin showed MIC and MBC of 1 and 6 µg/mL). Treatment with BoEA or ElAc increased survival of Tenebrio molitor larvae after lethal infection with Mabs and reduced carrageenan-induced paw edema in mice, around 40% of edema volume after the fourth hour, similarly to diclofenac. In conclusion, BoEA and ElAc exert antimicrobial effects against Mabs and have anti-inflammatory effects, making them potential sources of antimycobacterial drugs. The biological activities of ElAc may be due to its high binding affinities predicted for COX2 and DHFR enzymes.

Role of the YehD fimbriae in the virulence-associated properties of enteroaggregative Escherichia coli.

The interaction of enteroaggregative Escherichia coli (EAEC) strains with the colonic gut mucosa is characterized by the ability of the bacteria to form robust biofilms, to bind mucin, and induce a local inflammatory response. These events are mediated by a repertoire of five different aggregative adherence fimbriae variants (AAF/I-V) typically encoded on virulence plasmids. In this study, we report the production in EAEC strains of a new YehD fimbriae (YDF), which is encoded by the chromosomal gene cluster yehABCD, also present in most E. coli strains. Immuno-labelling of EAEC strain 042 with anti-AAF/II and anti-YDF antibodies demonstrated the presence of both AAF/II and YDF on the bacterial surface. We investigated the role of YDF in cell adherence, biofilm formation, colonization of spinach leaves, and induction of pro-inflammatory cytokines release. To this aim, we constructed yehD deletion mutants in different EAEC backgrounds (strains 17-2, 042, 55989, C1010, 278-1, J7) each harbouring one of the five AAFs. The effect of the YDF mutation was strain dependent and AAF independent as the lack of YDF had a different impact on the phenotypes manifested by the different EAECs tested. Expression of the yehABCD operon in a E. coli K12 ORN172 showed that YDF is important for biofilm formation but not for adherence to HeLa cells. Lastly, screening of pro-inflammatory cytokines in supernatants of Caco-2 cells infected with EAEC strains 042 and J7 and their isogenic ΔyehD mutants showed that these mutants were significantly defective in release of IL-8 and TNF-α. This study contributes to the understanding of the complex and diverse mechanisms of adherence of EAEC strains and identifies a new potential target for preventive measures of gastrointestinal illness caused by EAEC and other E. coli pathogroups.

Genomic Analysis of Limosilactobacillus fermentum ATCC 23271, a Potential Probiotic Strain with Anti-Candida Activity.

Limosilactobacillus fermentum (ATCC 23271) was originally isolated from the human intestine and has displayed antimicrobial activity, primarily against Candida species. Complete genome sequencing and comparative analyses were performed to elucidate the genetic basis underlying its probiotic potential. The ATCC 23271 genome was found to contain 2,193,335 bp, with 2123 protein-coding sequences. Phylogenetic analysis revealed that the ATCC 23271 strain shares 941 gene clusters with six other probiotic strains of L. fermentum. Putative genes known to confer probiotic properties have been identified in the genome, including genes related to adhesion, tolerance to acidic pH and bile salts, tolerance to oxidative stress, and metabolism and transport of sugars and other compounds. A search for bacteriocin genes revealed a sequence 48% similar to that of enterolysin A, a protein from Enterococcus faecalis. However, in vitro assays confirmed that the strain has inhibitory activity on the growth of Candida species and also interferes with their adhesion to HeLa cells. In silico analyses demonstrated a high probability of the protein with antimicrobial activity. Our data reveal the genome features of L. fermentum ATCC 23271, which may provide insight into its future use given the functional benefits, especially against Candida infections.

Molecular Detection of Drug-Resistance Genes of blaOXA-23-blaOXA-51 and mcr-1 in Clinical Isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa has caused high rates of mortality due to the appearance of strains with multidrug resistance (MDR) profiles. This study aimed to characterize the molecular profile of virulence and resistance genes in 99 isolates of P. aeruginosa recovered from different clinical specimens. The isolates were identified by the automated method Vitek2, and the antibiotic susceptibility profile was determined using different classes of antimicrobials. The genomic DNA was extracted and amplified by multiplex polymerase chain reaction (mPCR) to detect different virulence and antimicrobial resistance genes. Molecular typing was performed using the enterobacterial repetitive intergenic consensus (ERIC-PCR) technique to determine the clonal relationship among P. aeruginosa isolates. The drug susceptibility profiles of P. aeruginosa for all strains showed high levels of drug resistance, particularly, 27 (27.3%) isolates that exhibited extensively drug-resistant (XDR) profiles, and the other isolates showed MDR profiles. We detected the polymyxin E (mcr-1) gene in one strain that showed resistance against colistin. The genes that confer resistance to oxacillin (blaOXA-23 and blaOXA-51) were present in three isolates. One of these isolates carried both genes. As far as we know from the literature, this is the first report of the presence of blaOXA-23 and blaOXA-51 genes in P. aeruginosa.

Evaluation of Growth, Viability, Lactic Acid Production and Anti-Infective Effects of Lacticaseibacillus rhamnosus ATCC 9595 in Bacuri Juice (Platonia insignis).

Fruit juices have been emerging as excellent vehicles for development of probiotic products due to their nutritional properties and presence of bioactive compounds. This work evaluated the growth and viability of Limosilactobacillus fermentum ATCC 23271 and Lacticaseibacillus rhamnosus ATCC 9595 in bacuri juice (Platonia insignis Mart., Clusiaceae). Both strains were able to grow in bacuri juice, without any supplementation. Viability was kept after 28 days of storage; however, growth was significantly higher for L. rhamnosus ATCC 9595 (7.40 ± 0.04 Log CFU/mL). Following this, the effects of bacterial inoculum and pulp concentration on growth and lactic acid production by L. rhamnosus ATCC 9595 were investigated using a central composite rotational design. The inoculum concentration was the main factor for obtaining the most favorable relation between growth and organic acid production (G/pH ratio). Among the tested conditions, those used in assay 6 allowed the best G/pH ratio (2.13) and higher lactic acid production (4.14 g/L). In these conditions, L. rhamnosus ATCC 9595 grown in bacuri juice showed the same resistance towards acidification or addition of lysozyme than when cultivated in MRS. Finally, the anti-infective effects of fermented and non-fermented juices were analyzed using Tenebrio molitor larvae infected by enteroaggregative Escherichia coli 042. The pre-treatment with supernatants of both fermented and non-fermented juices significantly increased the survival of E. coli-infected larvae. However, only the L. rhamnosus-fermented juice had protective effects when inoculated 2 h after infection. Collectively, the results obtained in this research allowed the basis for the development of a non-dairy probiotic product from bacuri juice.

Monitoring of Peripheral Blood Leukocytes and Plasma Samples: A Pilot Study to Examine Treatment Response to Leflunomide in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a painful inflammatory disease of the joints which affects a considerable proportion of the world population, mostly women. If not adequately treated, RA patients can become permanently disabled. Importantly, not all the patients respond to the available anti-rheumatic therapies, which also present diverse side effects. In this context, monitoring of treatment response is pivotal to avoid unnecessary side effects and costs towards an ineffective therapy. Herein, we performed a pilot study to investigate the potential use of flow cytometry and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy as measures to identify responders and non-responders to leflunomide, a disease-modifying drug used in the treatment of RA patients. The evaluation of peripheral blood CD62L+ polymorphonuclear cell numbers and ATR-FTIR vibrational modes in plasma were able to discriminate responders to leflunomide (LFN) three-months after therapy has started. Overall, the results indicate that both flow cytometry and ATR-FTIR can potentially be employed as additional measures to monitor early treatment response to LFN in RA patients.

Role of the YehD fimbriae in the virulence-associated properties of enteroaggregative Escherichia coli

The interaction of enteroaggregative Escherichia coli (EAEC) strains with the colonic gut mucosa is characterized by the ability of the bacteria to form robust biofilms, to bind mucin, and induce a local inflammatory response. These events are mediated by a repertoire of five different aggregative adherence fimbriae variants (AAF/I-V) typically encoded on virulence plasmids. In this study, we report the production in EAEC strains of a new YehD fimbriae (YDF), which is encoded by the chromosomal gene cluster yehABCD, also present in most E. coli strains. Immuno-labelling of EAEC strain 042 with anti-AAF/II and anti-YDF antibodies demonstrated the presence of both AAF/II and YDF on the bacterial surface. We investigated the role of YDF in cell adherence, biofilm formation, colonization of spinach leaves, and induction of pro-inflammatory cytokines release. To this aim, we constructed yehD deletion mutants in different EAEC backgrounds (strains 17-2, 042, 55989, C1010, 278-1, J7) each harbouring one of the five AAFs. The effect of the YDF mutation was strain dependent and AAF independent as the lack of YDF had a different impact on the phenotypes manifested by the different EAECs tested. Expression of the yehABCD operon in a E. coli K12 ORN172 showed that YDF is important for biofilm formation but not for adherence to HeLa cells. Lastly, screening of pro-inflammatory cytokines in supernatants of Caco-2 cells infected with EAEC strains 042 and J7 and their isogenic ΔyehD mutants showed that these mutants were significantly defective in release of IL-8 and TNF-α. This study contributes to the understanding of the complex and diverse mechanisms of adherence of EAEC strains and identifies a new potential target for preventive measures of gastrointestinal illness caused by EAEC and other E. coli pathogroups.

Evaluación de la actividad antimicrobiana de los dentífricos basados en propóleos en patógenos orales / Evaluation of the antimicrobial activity of propolis toothpastes on oral pathogens / Avaliação da atividade antimicrobial de dentífricos com base em própolis em patógenos orais

Resumen Introducción y objetivo: La incorporación de propóleos en los dentífricos tiene como objetivo ayudar de manera más efectiva al control y la prevención de patologías orales a través de la eliminación de los patógenos presentes en la biopelícula. Sin embargo, se sabe poco sobre la eficacia antimicrobiana de diferentes productos en el mercado de microorganismos para estas patologías. El objetivo de este estudio fue investigar la acción antimicrobiana de tres dentífricos que contienen propóleos sobre los patógenos orales. Material y métodos: Se utilizó el método de difusión en agar para analizar tres dentífricos basados en propóleos, que incluyen: Noplak Max®, Protta® y Forever Bright®. Se utilizó un dentífrico sin propóleos (Malvatrikids®) como control negativo. Los controles positivos fueron 0,2% de clorhexidina diluida adicionalmente al 30% para igualar la concentración de clorhexidina de uno de los dentífricos evaluados, y el extracto de propóleos (Apis Flora®) al 11%. Para la determinación de la actividad antimicrobiana se utilizaron las cepas de Fusobacterium nucleatum y Aggregatibacter actinomycetemcomitans, Enterococcus faecalis, Streptococcus mutans, Lactobacillus acidophilus y Candida albicans. Resultados: De los dentífricos probados, Protta® y Forever Bright® mostraron acción inhibitoria contra S. mutans, E. faecalis y microorganismos de C. albicans. El dentífrico Nopla k® mostró baja actividad antimicrobiana, limitándose a S. mutans y E. faecalis. Cuando hubo un efecto antimicrobiano, los diámetros de los halos de inhibición del crecimiento variaron de 9mm a 28,83mm. Conclusión: El uso de un dentífrico que contiene propóleos para su uso eventual como complemento terapéutico en odontología está justificado, considerando las actividades farmacológicas.

Abstract Introduction and objective: The incorporation of propolis in dentifrices aims to more effectively assist the control and prevention of oral pathologies through the elimination of pathogens present in the biofilm. However, little is known about the antimicrobial efficacy of different products on the market for microorganisms for these conditions. The aim of this study was to investigate the antimicrobial action of three propolis-containing dentifrices on oral pathogens. Material and methods: The agar diffusion method was used to analyze three propolis-based dentifrices, including: Noplak Max®, Protta® and Forever Bright®. A non-propolis dentifrice (Malvatrikids®) was employed as a negative control. Positive controls were 0.2% chlorhexidine, further diluted 30% to match the chlorhexidine concentration of one of the evaluated dentifrices and 11% propolis extract (Apis Flora®). For the determination of antimicrobial activity the strains of Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans, Enterococcus faecalis, Streptococcus mutans, Lactobacillus acidophilus and Candida albicans were used. Results: Of the tested dentifrices, Protta® and Forever Bright® showed inhibitory action against S. mutans, E. faecalis and C. albicans microorganisms. Noplak® dentifrice showed low antimicrobial activity, being limited to S. mutans and E. faecalis. When there was an antimicrobial effect, the diameter of the growth inhibition halos ranged from 9mm to 28.83mm. Conclusion: The use of a propolis-containing dentifrice for eventual use as a therapeutic adjunct in dentistry is fully justified, considering the pharmacological activities.

Resumo Introdução e objetivo: A incorporação de própolis em dentifrícios visa ajudar a controlar e prevenir patologias bucais de maneira mais eficaz, através da eliminação de patógenos presentes no biofilme. No entanto, pouco se sabe sobre a eficácia antimicrobiana de diferentes produtos no mercado de microrganismos para essas patologias. O objetivo deste estudo foi investigar a ação antimicrobiana de três dentifrícios contendo própolis em patógenos orais. Material e métodos: O método de difusão em ágar foi utilizado para analisar três dentífricos à base de própolis, incluindo: Noplak Max®, Protta® e Forever Bright®. Um creme dental não própolis (Malvatrikids®) foi usado como controle negativo. Os controles positivos foram 0,2% de clorexidina diluída para 30% para corresponder à concentração de clorexidina de um dos dentifrícios avaliados e 11% de extrato de própolis (Apis Flora®). Para a determinação da atividade antimicrobiana, foram utilizadas as linhagens Fusobacterium nucleatum e Aggregatibacter actinomycetemcomitans, Enterococcus faecalis, Streptococcus mutans, Lactobacillus acidophilus e Candida albicans. Resultados: Dos dentifrícios testados, Protta® e Forever Bright® apresentaram ação inibitória contra S. mutans, E. faecalis e microorganismos de C. albicans. O creme dental Noplak® apresentou baixa atividade antimicrobiana, limitada a S. mutans e E. faecalis. Quando houve efeito antimicrobiano, os diâmetros dos halos de inibição de crescimento variaram de 9 a 28,83 mm. Conclusão: O uso de um dentifrício contendo própolis para eventual uso como complemento terapêutico em odontologia é totalmente justificado, considerando as atividades farmacológicas.

Antimicrobial Potential of Streptomyces ansochromogenes (PB3) Isolated From a Plant Native to the Amazon Against Pseudomonas aeruginosa.

The objective of this study was to evaluate the antibacterial action of filamentous bacteria isolated from the Byrsonima crassifolia leaf. An endophytic bacterium has been identified by classical and molecular techniques as Streptomyces ansochromogene. Screening for antibacterial action against pathogens with medical relevance (Klebsiella pneumoniae ATCC 700603, Pseudomonas aeruginosa ATCC 15692, Staphylococcus aureus ATCC 6538, Corynebacterium diphtheriae ATCC 27012, Mycobacterium abscessus, Cryptococcus gattii ATCC 24065, and Cryptococcus neoformans ATCC 24067) demonstrated activity against the bacterium P. aeruginosa ATCC 0030 with inhibition diameter zones (IDZ) of 17.6 ± 0.25 mm in the preliminary screening in solid medium. After fermentation in liquid medium, an IDZ of 19.6 ± 0.46 mm and a minimum inhibitory concentration (MIC) of 0.5 mg/mL were detected. The antibiofilm action was observed with 100% inhibition of biofilm formation at a concentration of 0.250 mg/mL. When the infection curve was prepared, it was observed that the metabolite was effective in protecting the larvae of Tenebrio molitor. The metabolite does not show toxicity for eukaryotic cells. The leishmanicidal activity demonstrated that the metabolite presented a dose-dependent effect on the promastigotes forms of Leishmania amazonensis growth and the estimated IC50/72 h was 71.65 ± 7.4 µg/mL. Therefore, it can be concluded that the metabolite produced by the endophytic bacterium Streptomyces sp. is promising for future use as an alternative strategy against bacterial resistance.

Cuminaldehyde potentiates the antimicrobial actions of ciprofloxacin against Staphylococcus aureus and Escherichia coli.

Escherichia coli and Staphylococcus aureus are important agents of urinary tract infections that can often evolve to severe infections. The rise of antibiotic-resistant strains has driven the search for novel therapies to replace the use or act as adjuvants of antibiotics. In this context, plant-derived compounds have been widely investigated. Cuminaldehyde is suggested as the major antimicrobial compound of the cumin seed essential oil. However, this effect is not fully understood. Herein, we investigated the in silico and in vitro activities of cuminaldehyde, as well as its ability to potentiate ciprofloxacin effects against S. aureus and E. coli. In silico analyses were performed by using different computational tools. The PASS online and SwissADME programmes were used for the prediction of biological activities and oral bioavailability of cuminaldehyde. For analysis of the possible toxic effects and the theoretical pharmacokinetic parameters of the compound, the Osiris, SwissADME and PROTOX programmes were used. Estimations of cuminaldehyde gastrointestinal absorption, blood brain barrier permeability and skin permeation by using SwissADME; and drug likeness and score by using Osiris, were also evaluated The in vitro antimicrobial effects of cuminaldehyde were determined by using microdilution, biofilm formation and time-kill assays. In silico analysis indicated that cuminaldehyde may act as an antimicrobial and as a membrane permeability enhancer. It was suggested to be highly absorbable by the gastrointestinal tract and likely to cross the blood brain barrier. Also, irritative and harmful effects were predicted for cuminaldehyde if swallowed at its LD50. Good oral bioavailability and drug score were also found for this compound. Cuminaldehyde presented antimicrobial and anti-biofilm effects against S. aureus and E. coli.. When co-incubated with ciprofloxacin, it enhanced the antibiotic antimicrobial and anti-biofilm actions. We suggest that cuminaldehyde may be useful as an adjuvant therapy to ciprofloxacin in S. aureus and E. coli-induced infections.

Effect of Silver Diamine Fluoride on the Bonding Properties to Caries-affected Dentin.

PURPOSE: To evaluate 1. the microtensile bond strength (µTBS) and in situ degree of conversion (DC) of adhesives applied using two bonding strategies after silver diamine fluoride (diamine) application on carious dentinal lesions, and 2. dentin etching patterns using SEM and energy dispersive x-ray spectroscopy. MATERIALS AND METHODS: Human molars were randomly divided into 12 experimental groups according to: 1. application of a silver diamine fluoride solution (carious dentinal lesion without silver diamine fluoride treatment [control], with 12% silver diamine fluoride [diamine 12%] or 38% silver diamine fluoride [diamine 38%]); 2. adhesives (Clearfil Universal Bond Quick [CUQ] and Scotchbond Universal [SBU]); 3. adhesive strategy (etch-and-rinse [ER] and self-etch [SE]). After restoration, the specimens were sectioned and submitted to µTBS testing. Sticks from each tooth were used for DC evaluation. To examine the changes induced by diamine before and after phosphoric acid treatment, SEM/EDX analysis was performed. Data from the µTBS and DC tests were analyzed using three-way ANOVA and Tukey's test (α = 0.05). RESULTS: Both concentrations of diamine resulted in a statistically significantly higher mean µTBS compared to the control (p < 0.0001). Diamine 38% showed a statistically significantly higher mean µTBS for both adhesives in SE mode compared to diamine 12% (p < 0.0001). The application of diamine to carious dentinal lesions did not significantly influence the mean DC values for either adhesive (p = 0.72). SBU showed a higher mean DC compared to CUQ (p = 0.03). After diamine treatment, there was an increase in the Ca peak intensity and the presence of residual silver ions mainly when diamine 38% was applied along with the SE approach. CONCLUSION: Independent of the adhesive application approach, the use of diamine may be a promising alternative to increase µTBS without jeopardizing the DC of the two adhesives in carious dentinal lesions.

Corrigendum: Cinnamaldehyde Inhibits Staphylococcus aureus Virulence Factors and Protects against Infection in a Galleria mellonella Model.

[This corrects the article DOI: 10.3389/fmicb.2016.02052.].

Antifungal and Antivirulence Activity of Vaginal Lactobacillus Spp. Products against Candida Vaginal Isolates.

Candida yeasts are generally found in the vaginal microbiota; however, disruption of the balance maintained by host factors and microorganisms results in vulvovaginal candidiasis (VVC). This study evaluated the antagonistic activity of vaginal Lactobacillus spp. on Candida albicans to verify whether active compounds of Lactobacillus spp. had antifungal and antivirulence activity. The antagonism assay showed that 15 out of 20 Lactobacillus strains had an inhibitory effect on C. albicans. Biosurfactants displayed surface-tension-reducing activity, with the best value obtained for Lactobacillus gasseri 1. Lactobacillus rhamnosus ATCC 9595, Lactobacillus acidophilus ATCC 4356, and Lactobacillus paracasei 11 produced biosurfactants that decreased C. albicans adhesion and disrupted biofilm formation. The best results were obtained in the pre-incubation assay for L. gasseri 1 and L. paracasei 11. Overall, Lactobacillus strains showed significant anti-Candida activity, and their biosurfactants exhibited considerable anti-adhesion and antibiofilm activity against C. albicans. To be considered safe for use in vivo, the safety of biosurfactant (BS) should be investigated using cytotoxicity assays.