Exploring Ubiquinone Biosynthesis Inhibition as a Strategy for Improving Atovaquone Efficacy in Malaria.

Atovaquone (AV) acts on the malaria parasite by competing with ubiquinol (UQH2) for its union to the mitochondrial bc1 complex, preventing the ubiquinone-8 and ubiquinone-9 (UQ-8 and UQ-9) redox recycling, which is a necessary step in pyrimidine biosynthesis. This study focused on UQ biosynthesis in Plasmodium falciparum and adopted proof-of-concept research to better elucidate the mechanism of action of AV and improve its efficacy. Initially, UQ biosynthesis was evaluated using several radioactive precursors and chromatographic techniques. This methodology was suitable for studying the biosynthesis of both UQ homologs and its redox state. Additionally, the composition of UQ was investigated in parasites cultivated at different oxygen saturations or in the presence of AV. AV affected the redox states of both UQ-8 and UQ-9 homologs by increasing the levels of the respective reduced forms. Conversely, low-oxygen environments specifically inhibited UQ-9 biosynthesis and increased the antimalarial efficacy of AV. These findings encouraged us to investigate the biological importance and the potential of UQ biosynthesis as a drug target based on its inhibition by 4-nitrobenzoate (4-NB), a 4-hydroxybenzoate (4-HB) analog. 4-NB effectively inhibits UQ biosynthesis and enhances the effects of AV on parasitic growth and respiration rate. Although 4-NB itself exhibits poor antimalarial activity, its 50% inhibitory concentration (IC50) value increased significantly in the presence of a soluble UQ analog, p-aminobenzoic acid (pABA), or 4-HB. These results indicate the potential of AV combined with 4-NB as a novel therapy for malaria and other diseases caused by AV-sensitive pathogens.

An overview on the molecular diagnosis of animal leptospirosis.

The most common presentation of animal leptospirosis is the subclinical and silent chronic form, that can lead to important reproductive disorders. The diagnosis of this chronic form remains a challenge. The aim of the present study is to gather and critically analyse the current information about molecular tools applied to animal leptospirosis diagnosis, particularly the silent chronic presentation of the infection. Regarding clinical specimens, samples from urinary tract were the most used (69/102, 67·7%), while few studies (12/102, 11·8%) investigated samples from reproductive tract. Concerning the molecular methods applied, the most used is still the conventional polymerase chain reaction (PCR) (46/102, 45%), followed by real-time PCR (38/102, 37·2%). The lipL32 gene is currently the most common target used for Leptospira detection, with 48% of studies applying this genetic marker. From all the studies, only few (21/102, 20·5%) performed gene sequencing. According to the majority of authors, current evidence suggests that lipL32-PCR is useful for an initial screening for Leptospira DNA detection in animal clinical samples. Posteriorly, if DNA sequencing could be performed on positive lipL32-PCR samples, we encourage the use of secY gene as a genetic marker. The molecular methods appear as the most important tools for the diagnosis of the chronic silent leptospirosis on domestic animals, reinforcing its evident impact not only on animal reproduction but also on a One Health context.

High-touch surfaces: microbial neighbours at hand.

Despite considerable efforts, healthcare-associated infections (HAIs) continue to be globally responsible for serious morbidity, increased costs and prolonged length of stay. Among potentially preventable sources of microbial pathogens causing HAIs, patient care items and environmental surfaces frequently touched play an important role in the chain of transmission. Microorganisms contaminating such high-touch surfaces include Gram-positive and Gram-negative bacteria, viruses, yeasts and parasites, with improved cleaning and disinfection effectively decreasing the rate of HAIs. Manual and automated surface cleaning strategies used in the control of infectious outbreaks are discussed and current trends concerning the prevention of contamination by the use of antimicrobial surfaces are taken into consideration in this manuscript.

Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response.

AIMS: A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. METHODS AND RESULTS: After immunization, cytokine and immunoglobulin profiles were measured. The BCG prime L. lactis FnBPA+ (pValac:ESAT-6) boost group was the most responsive group, with a significant increase in splenic pro-inflammatory cytokines IL-17, IFN-γ, IL-6 and TNF-α compared with the negative control. CONCLUSIONS: Based on the results obtained here, we demonstrated that L. lactis FnBPA+ (pValac:ESAT-6) was able to increase the BCG vaccine general immune response. SIGNIFICANCE AND IMPACT OF THE STUDY: This work is of great scientific and social importance because it represents the first step towards the development of a booster to the BCG vaccine using L. lactis as a DNA delivery system.

Identification of differentially expressed genes in pathways of cerebral neurotransmission of anovulatory mice.

Polycystic ovary syndrome is the classic example of loss of functional cyclicity and anomalous feedback. In this case, the excessive extra-glandular production and conversion of androgens to estrogens are the pathophysiological basis of the chronic anovulation. The literature describes an experimental model of the polymicrocystic ovary in obese diabetic mice with insulin resistance. The fact that these animals exhibit obesity, insulin resistance, and infertility demonstrates their skill as an experimental model for polycystic ovary. A recent study using long protocol for up to 40 weeks showed that anovulatory and obese mice transplanted with adipose tissue from animals with normal weight have multiple changes in their phenotype. These changes include reduction of body weight, prevention of obesity, insulin level normalization, and insulin tolerance tests, preventing the elevation of steroids and especially the reversal of fertility restoration with anovulation. Considering that there are close relationships between the ovulation process and the central nervous system, we propose to evaluate the gene expression levels of 84 different genes involved in neurotransmission and insulin pathways in addition to examining the neurolipidosis differential murine brain before and after reversal of anovulation. The present study showed changes in gene expression of molecular markers in brain tissue of animals for brain neurotransmission pathways as well as pathways for insulin. GABAergic genes, muscarinic, serotonin receptors, receptor tyrosine kinase, and genes of interleukin 6 showed overexpression profile. There was also a change in the lipid content in anovulatory brain, obesity, and insulin resistant mice (Ob-/Ob-) compared with controls. The re-introduction of leptin in these animals appears to reverse, at least in part, this profile.

Copper and zinc affect the activity of plasma membrane H+-ATPase and thiol content in aquatic fungi.

Aquatic hyphomycetes are the major microbial decomposers of plant litter in streams. We selected three aquatic hyphomycete species with different abilities to tolerate, adsorb and accumulate copper and zinc, and we investigated the effects of these metals on H+-ATPase activity as well as on the levels of thiol (SH)-containing compounds. Before metal exposure, the species isolated from a metal-polluted stream (Heliscus submersus and Flagellospora curta) had higher levels of thiol compounds than the species isolated from a clean stream (Varicosporium elodeae). However, V. elodeae rapidly increased the levels of thiols after metal exposure, emphasizing the importance of these compounds in fungal survival under metal stress. The highest amounts of metals adsorbed to fungal mycelia were found in the most tolerant species to each metal, i.e. in H. submersus exposed to copper and in V. elodeae exposed to zinc. Short-term (10 min) exposure to copper completely inhibited the activity of H+-ATPase of H. submersus and V. elodeae, whilst zinc only led to a similar effect on H. submersus. However, at longer exposure times (8 days) the most metal-tolerant species exhibited increased H+-ATPase activities, suggesting that the plasma membrane proton pump may be involved in the acclimation of aquatic hyphomycetes to metals.

Reproductive strategies in two inseminating species of Glandulocaudini, Mimagoniates microlepis and Mimagoniates rheocharis (Characiformes: Characidae: Stevardiinae).

The reproductive biology of two inseminating Glandulocaudini species, Mimagoniates microlepis and Mimagoniates rheocharis, was investigated and compared with reproductive patterns described for other inseminating and non-inseminating characids, hypothesizing the evolutionary history of these reproductive traits. The long reproductive period, with higher activity in colder months, distinguishes the reproductive strategy of these species when compared with most characiforms. The M. rheocharis population was structured in two groups of males throughout the year, mature males with high gonado-somatic index (IG = 2·0 and 4·4) and immature and maturing males with low IG values (0·0 and 1·2). Mimagoniates rheocharis and M. microlepis showed the lowest absolute mean fecundities known for characids, indicating that inseminating species allocate less energy to oocyte production and reinforcing the hypothesis that insemination has an adaptive advantage, which provides a higher chance of fertilization.

First record of the anisakid nematode Anisakis nascettii in the Gervais' beaked whale Mesoplodon europaeus from Brazil.

Anisakid nematodes are parasites with an indirect life cycle, involving many hosts, including cetaceans that act as definitive hosts. Identification at species level is crucial for a better understanding of the epidemiology and ecology of these parasites, but an accurate diagnosis based only on morphology is difficult. In Brazil, genetic characterization of anisakids is still rare, with Anisakis typica and A. physeteris being the only two species identified by genetic markers until now. The definitive hosts of A. nascettii are Mesoplodon grayi, M. bowdoini, M. layardii and M. mirus. Geographical locations of A. nascettii include the coasts of New Zealand, South Africa and Europe. In this study, a nematode was collected from a Gervais' beaked whale, Mesoplodon europaeus, stranded in Ceará State, north-east Brazil. Genetic analysis based on 18S rDNA, internal transcribed spacer (ITS) region and mtDNA cox2 gene revealed 100% identity with Anisakis sp. U94365, 99% with Anisakis sp. (MP-2005 EU718477 A. nascettii) and 99% with A. nascettii DQ116431, respectively. Phylogenetic analyses of ITS and cox2 sequences using both neighbour-joining and maximum-likelihood methods provided strong support for a clade with only A. nascettii specimens. This study demonstrated for the first time the identification of A. nascettii in the Brazilian Atlantic Coast, revealing a wider geographical distribution of this parasite worldwide and extending the range of its definitive hosts to a new Mesoplodon species, M. europaeus, the Gervais' beaked whale.

Malignant syphilis in an AIDS patient.

Malignant syphilis is an uncommon, but not unknown, ulcerative variation of secondary syphilis. The lesions typically begin as papules, which quickly evolve to pustules and then to ulcers with elevated edges and central necrosis. It is usually, but not mandatory, found in patients with some level of immunosuppression, such as HIV patients, when the TCD4(+) cell count is >200 cells/mm(3). Despite the anxiety the lesions cause, this form of the disease has a good prognosis. The general symptoms disappear right after the beginning of treatment, and lesions disappear over a variable period. This study reports the case of a 27-year-old man who has been HIV positive for 6 years, uses antiretroviral therapy incorrectly, has a TCD4(+) cell count of 340 cells/mm(3), a VDRL of 1:128 and itchy disseminated hyperchromic maculopapular lesions with rupioid crusts compatible with malignant syphilis.

Prospective uses of recombinant Lactococcus lactis expressing both listeriolysin O and mutated internalin A from Listeria monocytogenes as a tool for DNA vaccination.

In this study, Lactococcus lactis was engineered to express mutated internalin A on its surface and to secrete large amounts of listeriolysin O (LLO) in order to improve its potential as a vehicle for DNA vaccination. Western blotting experiments demonstrated that the bacterium expressed LLO in both the cytoplasmic and extracellular compartments, with higher quantities found in the culture supernatants. A hemolytic assay showed that the recombinant strain secreted 250 ng active LLO/mg total protein. This mInlA/LLO-producing strain of L. lactis may be used as an alternative tool in DNA vaccination against a number of infectious diseases or in cancer therapy.

Correlation between the cariogenic response in biofilms generated from saliva of mother/child pairs.

This study aimed to correlate the cariogenic responsiveness of biofilms generated from the saliva of mothers and children. The mother-child pairs were classified according to the children's caries levels: caries-free, early childhood caries (ECC) or severe ECC. Microcosm biofilms were grown on enamel discs for 10 days. Factors under evaluation were caries experience levels, inoculum source (mothers and children) and growth conditions including cariogenic challenge (growth medium provided with and without sucrose) and no cariogenic challenge (growth medium sucrose-free). Statistical analysis was performed with ANOVA and Tukey's test, and the Spearman correlation test. Regular sucrose exposure resulted in a higher surface hardness change (%SHC). The correlation between biofilms formed from saliva of mother-child pairs was significant regarding pH, total aciduric microorganisms and lactobacilli counts under cariogenic challenge. Biofilm growth originating from mother-child pairs under regular sucrose exposure promoted the same cariogenic response independently of caries experience and the microbiological profile of the donors.

Effect of yogurt containing Bifidobacterium animalis subsp . lactis DN-173010 probiotic on dental plaque and saliva in orthodontic patients.

AIM: To assess how consumption of yogurt containing Bifidobacterium animalis subsp. lactis DN-173010 probiotic for a period of 2 weeks affects salivary and dental plaque levels of mutans streptococci and lactobacilli in patients undergoing orthodontic treatment. METHODS: A crossover, double-blind, randomized and placebo-controlled clinical trial was performed with 26 volunteers. The study was divided into four periods. During periods 2 and 4, the volunteers ingested yogurt containing probiotic or control yogurt daily for 2 weeks. Periods 1 and 3 were a 1-week run-in period and 4-week washout period, respectively. Saliva and dental plaque samples were collected from each participant at the end of each period. Mutans streptococci, lactobacilli, and total cultivable microorganisms were counted. Values were compared between groups and across periods with the Wilcoxon's test. RESULTS: There was no difference between the yogurt containing probiotic and the control yogurt for any of the studied variables (all p > 0.05). A reduction in counts of total cultivable microorganisms was observed in dental plaque samples after ingestion of either yogurts (both p < 0.05 vs. baseline), but not in saliva (p < 0.05). CONCLUSION: Daily ingestion of yogurt with or without B. animalis subsp. lactis for a period of 2 weeks was beneficial in reducing total microbial counts in dental plaque. Therefore, no additional benefits were achieved by the use of the tested probiotic strain.

Dental pain in Brazilian preschool children: association with the severity of dental caries and impact on oral health-related quality of life.

PURPOSE: This study aimed to verify the association between dental pain and severity of dental caries (caries morbidity stages) and the impact on oral health-related quality of life (OHRQoL) in preschool children. METHODS: A cross-sectional study with 199 children (2-5 years old) enrolled at preschools in Capão do Leão-RS, Brazil. The self-report of mothers of children with a history of dental pain in the last 6 months and perception of their child's OHRQoL (ECOHIS) were obtained through a structured questionnaire. This questionnaire also collected independent variables. Children's oral examination was performed using the CAST instrument to determine caries morbidity stage. Crude and adjusted Poisson regression analysis was performed. RESULTS: The prevalence of dental pain was 14.57%. The chance of the occurrence of dental pain was higher among children diagnosed in morbidity [Prevalence ratio-PR: 5.29 (95% confidence interval-95% CI 1.91-14.61); p = 0.001] and severe morbidity [RP = 6.12 (95 CI% 2.25-16.64); p < 0.001] stages. Children with dental pain presented higher scores in the total ECOHIS [rate ratio = 7.11 (95% CI 4.55-11.09); p < 0.001] and in all of the domains of this instrument. Furthermore, children with a history of dental trauma [PR = 2.41 (95% CI 1.15-5.04); p < 0.001] and those whose reason for last visit to the dental office was for restorative/endodontic/extraction treatment [PR = 1.29 (95% CI 1.01-6.19); p = 0.049] had a higher prevalence of dental pain. CONCLUSION: A substantial prevalence of dental pain in the last 6 months and negative impact on children's OHRQoL was identified in this sample. Children diagnosed with carious dentin lesions and abscess and fistula were more likely to have dental pain.

Placental abnormalities associated with Leptospira interrogans infection in naturally infected mares.

The reproductive features of equine leptospirosis are often neglected. Equine genital leptospirosis is characterized as a silent chronic syndrome, and besides abortions, leads to placental abnormalities, stillbirths, and birth of weak foals. This study aimed to study the occurrence of placental abnormalities associated with Leptospira interrogans infection in naturally infected mares under field conditions. The studied herd had a high occurrence of placentitis and abortions. Ten pregnant mares, eight with placental abnormalities on ultrasonography and were selected. Serum and cervicovaginal mucus (CVM) samples were collected for serology and PCR, respectively. Positive samples in lipL32-PCR were submitted to the sequencing of the secY gene. In lipL32-PCR of CVM, five out of 10 (50%) mares were positive and all were characterized as Leptospira interrogans. Our results highlight the presence of placental abnormalities in the reproductive subclinical leptospirosis syndrome. We encourage field veterinarians to include leptospirosis testing in their reproductive management.

Evaluation of the antimicrobial activity of Eucalyptus radiata essential oil against Escherichia coli strains isolated from meat products.

The present study sought to evaluate the antimicrobial and anti-adherent potential of Eucalyptus radiata essential oil against food-borne strains of Escherichia coli. The study was performed using the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). In addition, the disk diffusion technique was used to evaluate the association of Eucalyptus radiata essential oil with synthetic antimicrobials. The Minimum Inhibitory Adherence Concentration (MIC) was also performed. The results revealed that E. radiata showed antimicrobial activity against the E. coli strains tested, with MIC values ranging from 500 µg/mL to 1000 µg/mL and MBC values ranging from 500 µg/mL to 1,024 µg/mL. As for the associations, it was observed that E. radiata oil exhibited a synergistic effect for some antibiotics, especially Ceftriaxone, with greater interference from the essential oil. Furthermore, it was effective in inhibiting the adherence of bacterial strains of E. coli, showing a more significant antibiofilm effect than the antibacterial agent 0.12% chlorhexidine digluconate. In summary, the essential oil of E. radiata showed antimicrobial potential against strains of E. coli of food origin, and can therefore, through in-depth studies, be used alone or in association with synthetic antimicrobials to combat infections caused by this pathogen.

In vivo antibiofilm effect of cerium, chitosan and hamamelitannin against usual agents of catheter-related bloodstream infections.

OBJECTIVES: Catheter-related bloodstream infections (CRBSIs) are common healthcare-associated infections associated with increased morbidity and medical costs. Antiseptic- and antibiotic-coated central venous catheters (CVCs) have been proposed to reduce the incidence of CRBSIs, with variable success. The aim of this study was to determine the in vivo antibiofilm activity of biocompatible and inexpensive compounds, such as cerium nitrate, chitosan and hamamelitannin, against usual agents of CRBSIs. METHODS: The antibiofilm effect of cerium nitrate, chitosan and hamamelitannin was tested against Staphylococcus epidermidis, Staphylococcus aureus, Acinetobacter baumannii and Candida albicans in a mouse foreign body infection model, using polyurethane catheter segments. Biofilm formation was assessed with a crystal violet assay to quantify the total biomass, with a tetrazolium reduction assay to quantify the metabolic activity and with scanning electron microscopy. RESULTS: At subinhibitory concentrations, cerium nitrate significantly reduced biofilm formation by C. albicans, chitosan significantly decreased biofilm formation by S. epidermidis and C. albicans, and hamamelitannin significantly inhibited all bacterial biofilms. DISCUSSION: The in vivo antibiofilm effect of cerium nitrate against C. albicans and of chitosan against C. albicans and S. epidermidis, at subinhibitory concentrations, makes them promising alternatives to coat CVCs. Moreover, the microbicidal effect on a wider range of CVC colonizers was previously reported in vitro for both compounds, at higher concentrations. For all bacterial strains, the highest in vivo antibiofilm efficacy was achieved with hamamelitannin. For A. baumannii, this is the first report of in vivo inhibition.

Immunotherapy of allergic diseases using probiotics or recombinant probiotics.

Allergic diseases affect up to 30% of the western population, and their prevalence is increasing. Probiotics are able to modulate the mucosal immune response, and clinical trials demonstrated that specific strains, especially lactic acid bacteria (LAB) ones, reduce allergic symptoms. Moreover, the use of recombinant probiotics has been evaluated as possible strategies for the immunotherapy of allergic diseases. The production and delivery of allergens by recombinant LAB in concert with their ability to induce a Th1-type immune response have been shown to be a promising mucosal vaccination strategy in mouse model. The aim of this article is to review the applications of probiotics in allergy immunotherapy with a special focus on recombinant LAB delivering proteins or DNA.

Falls in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To determine the prevalence of falls in human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and possible factors associated to their occurrence. SETTING: Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz (FIOCRUZ) - Brazil. METHODS: Thirty-six HAM/TSP patients able to walk at least 20 m were assessed by a questionnaire. Data regarding gender, age, duration of disease (DD), HTLV-I proviral load (HPL), frequency of physical activity (FCA), use of walking aids, functional ambulation level, the number of falls and associated injuries in the last year were reviewed. Multiple correspondence analysis was used to group characteristics of this sample according to the fall occurrence. RESULTS: The prevalence of falls was 63.9% and we observed injuries in 47.8% of the cases. Four groups were identified in the descriptive analysis. One group was formed by faller individuals, men <60 years, independent ambulation, FCA≥3 times per week and HPL <6.6 copies per 100 cells (group B). The other one comprised non-faller patients, women ≥60 years, restricted ambulation, DD ≥7 years, use of orthosis, FCA 0-1 time per week and HPL ≥6.6 copies per 100 cells (group D). The others two groups comprised individuals that did not use orthosis (group A) and those that FCA was two times per week and DD <7 years (group C). CONCLUSION: Falls occur in roughly two-thirds of ambulatory HAM/TSP patients and are associated with significant morbidity. Further studies with a larger number of patients are necessarily to identify risk factors in order to elaborate specific programs to prevent falls in this population.

Influence of essential oils on the quality of Vigna unguiculata L. (Walp.) seeds compared by traditional method, image and multivariate analysis.

The extracts of medicinal plants are used for the treatment of seeds in order to reduce the action of phytopathogens and increase the vigor of the seeds. Currently, computerized image analysis has been used to assess the physiological quality of seed lots. The objective was to evaluate the efficiency of the Vigor-S® software in the evaluation of the physiological quality of cowpea seeds treated with essential oils, comparing with a traditional test and the principal component analysis. Two cowpea cultivars were analyzed, BRS Tumucumaque and BRS Guariba, treated with doses of natural extracts of Alfavaca, garlic, horsetail, citronella and pyroligneous acid. The traditional method consisted of evaluations for germination, first germination count, seedling emergence, emergence speed index, accelerated aging, fresh matter and dry matter of seedling and the image analysis for: seedling length, growth index, uniformity index, vigor index, and germination. A Principal component analysis was applied to reduce the number of variables. Horsetail, Alfavaca and citronella extracts were efficient in increasing the physiological quality of the seeds of at least one cultivar. The Vigor-S® software proved to be efficient compared to traditional tests to assess the physiological quality of seeds. Principal Component Analysis is an ally to identify the best extracts and doses to be used. The image analysis method proved to be effective when compared to the traditional method and can therefore be used.

Cerium, chitosan and hamamelitannin as novel biofilm inhibitors?

OBJECTIVES: The colonization of indwelling medical devices and subsequent biofilm formation represents a global challenge since it promotes the persistence of infection and contributes to antimicrobial resistance. The aim of this study was to determine the antimicrobial activity of cerium, chitosan and hamamelitannin against usual microbial colonizers and to assess their efficacy regarding biofilm formation on polyurethane (PUR)-like catheters. METHODS: The antimicrobial and anti-biofilm effect of cerium nitrate, low molecular weight chitosan (LMWC) and hamamelitannin was tested against Staphylococcus epidermidis, Staphylococcus aureus, Acinetobacter baumannii and Candida albicans strains. Biofilm formation was assessed with PUR-like catheter segments and the metabolic activity was quantified by colorimetry with a tetrazolium reduction assay. RESULTS: Cerium nitrate and LMWC inhibited the microbial growth of all microbial strains tested; hamamelitannin showed no inhibition. Regarding biofilm formation on PUR-like catheters, with subinhibitory concentrations: cerium nitrate significantly inhibited the metabolic activity of C. albicans; LMWC reduced the metabolic activity of S. epidermidis and C. albicans; and hamamelitannin decreased the metabolic activity of all tested bacteria, but not of yeasts. CONCLUSIONS: The microbicidal activity of cerium nitrate and LMWC was clearly demonstrated in this study, as was their fungistatic effect at lower concentrations. Hamamelitannin significantly reduced biofilm metabolic activity of all tested bacteria. These microbial inhibitors may play a promising role regarding different biomedical applications.