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Pathogenic microorganisms have adapted different strategies during the course of time to invade host defense mechanisms and overcome the effect of potent antibiotics. The formation of biofilm on both biotic and abiotic surfaces by microorganisms is one such strategy to resist and survive even in presence of antibiotics and other adverse environmental conditions. Biofilm is a safe home of microorganisms embedded within self-produced extracellular polymeric substances comprising of polysaccharides, extracellular proteins, nucleic acid, and water. It is because of this adaptation strategy that pathogenic microorganisms are taking a heavy toll on the health and life of organisms. In this review, we discuss the colonization of pathogenic microorganisms on tissues and medically implanted devices in human beings. We also focus on food spoilage, disease outbreaks, biofilm-associated deaths, burden on economy, and other major concerns of biofilm-forming pathogenic microorganisms in food industries like dairy, poultry, ready-to-eat food, meat, and aquaculture.
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Bactérias/patogenicidade , Fenômenos Fisiológicos Bacterianos , Biofilmes/crescimento & desenvolvimento , Indústria Alimentícia/economia , Animais , Aquicultura , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Indústria Alimentícia/métodos , Microbiologia de Alimentos , Humanos , Carne/microbiologia , Aves Domésticas/microbiologiaRESUMO
Neutrophils are the first infiltrating cell type essential for combating pneumoseptic infections by bacterial pathogens including Klebsiella pneumoniae (KPn). Following an infection or injury, removal of apoptotic infiltrates via a highly regulated process called efferocytosis is required for restoration of homeostasis, but little is known regarding the effect of bacterial infection on this process. Here we demonstrate that KPn infection impedes the efferocytic uptake of neutrophils in-vitro and in-vivo in lungs by macrophages. This impaired efferocytosis of infected neutrophils coincides with drastic reduction in the neutrophil surface exposure of apoptosis signature phospholipid phosphatidyserine (PS); and increased activity of phospholipid transporter flippases, which maintain PS in the inner leaflet of plasma membrane. Concomitantly, pharmacological inhibition of flippase activity enhanced PS externalization and restored the efferocytosis of KPn infected neutrophils. We further show that KPn infection interferes with apoptosis activation and instead activates non-apoptotic programmed cell death via activation of necroptosis machinery in neutrophils. Accordingly, pharmacological inhibition of necroptosis by RIPK1 and RIPK3 inhibitors restored the efferocytic uptake of KPn infected neutrophils in-vitro. Importantly, treatment of KPn infected mice with necroptosis inhibitor improved the disease outcome in-vivo in preclinical mouse model of KPn pneumonia. To our knowledge, this is the first report of neutrophil efferocytosis impairment by KPn via modulation of cell death pathway, which may provide novel targets for therapeutic intervention of this infection.
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Apoptose , Infecções por Klebsiella/imunologia , Klebsiella pneumoniae/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Fagocitose , Pneumonia/imunologia , Animais , Células Cultivadas , Infecções por Klebsiella/metabolismo , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/patologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Necrose , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Neutrófilos/patologia , Pneumonia/metabolismo , Pneumonia/microbiologia , Pneumonia/patologia , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismoRESUMO
Syzygium cumini L. Skeels (Myretacae family) is a native plant of the Indian subcontinent which has wide socio-economical importance and is well known for its ant diabetic activity. The present study aimed to investigate the antibiofilm activity of purified fraction (EA) from S. cumini leaf extract against P. aeruginosa and S. aureus. The EA did not show any effect on growth of P. aeruginosa and S. aureus at the concentration of 900 µg/ml. At this concentration EA showed biofilm inhibition up to 86 ± 1.19% (***P < 0.0001) and 86.40 ± 1.19% (***P < 0.0001) in P. aeruginosa and S. aureus respectively. SEM examination also confirmed the reduction in biofilm formation. Further EA also disrupted some virulence phenotypes in P. aeruginosa and S. aureus. Bioactive compounds detected by GC-MS showed their possible molecular interaction with RhlG/NADP active-site complex (PDB ID: 2B4Q), LasR-TP4 complex (PDB ID: 3JPU) and Pseudaminidase (PDB ID: 2W38) from P. aeruginosa. The in vitro biofilm inhibition, virulence factor inhibition and the mode of interaction of bioactive components in Syzygium cumini with QS proteins of bacteria reported in this study might be an affordable and effective alternative method of controlling quorum sensing/biofilm-associated infections.
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Evaluation of tender coconut water was done that was subjected to a nonthermal two stage microfiltration process that involved filtration through 0.8 µm and 0.45 µm pore size filters followed by addition of 200 mg/L citric acid, 180 mg/L ascorbic acid, orange honey at 5% (w/v) followed by packaging in glass bottles with headspace flushed with nitrogen. The effect of storage under refrigeration was studied. Microfiltration reduced the total simple sugars, protein and reducing sugars respectively by 13.4, 13.0 and 21.5% without significantly affecting the overall acceptability. Microfiltered samples did not show any signs of haemolytic activity. Addition of citric acid, ascorbic acid and honey was able to reduce activity of polyphenol oxidase and peroxidase and maintain product stability. Even though microfiltered samples were sterile for 190 days, the samples were acceptable for sensory attributes till day 90 of storage. Microfiltration and use of additives were thus found to increase the shelf life of tender coconut water.
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BACKGROUND & OBJECTIVES: Aedes aegypti is the most important vector of dengue virus infection in humans worldwide. Accurate identification and colonization are the essential requirements to understand vector biology as well as its diseases transmission potential. In this study, we have used molecular approaches for the identification of Ae. aegypti mosquitoes that were collected from the Pilani region of Rajasthan, India Methods: Field collected mosquito larvae were colonized under laboratory conditions. Conserved genetic markers, ITS-2 and mtCOI were used for amplification through species-specific primers to identify the mosquito species/ strain. Sequencing result of this strain was phylogenetically compared with other global strains through MEGA software. RESULTS: A comprehensive multiple sequence alignment and phylogenetic analysis revealed that COI gene of Ae. aegypti has extremely low genetic variability with one of the Indian isolate from Thirumala, Andhra Pradesh region (GenBank: HM807262.1). However, in context of different geographical locations, it indicated close similarity with Thailand's strain and high variability when compared with Madagascar strain. On the other hand, ITS-2 illustrated highest identity with Ae. aegypti of Saudi Arabia (GenBank: JX423807.1) whereas, high divergence was observed from Mayotte, France strain (GenBank: KF135506). INTERPRETATION & CONCLUSION: The findings suggest that this isolate from Rajasthan is similar to other Asian continent strains possibly due to the same origin. Understanding the vectorial capacity of these geographically distributed mosquito strains will enhance our knowledge to improve existing vector surveillance and control programme.
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Aedes/classificação , Aedes/genética , Variação Genética , Mosquitos Vetores , Aedes/crescimento & desenvolvimento , Animais , Análise por Conglomerados , Primers do DNA/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Índia , Larva/classificação , Larva/genética , Masculino , Filogenia , Análise de Sequência de DNARESUMO
Common cooking methods were used to prepare basmati rice products, including boiling 1 (boiling by absorption), boiling 2 (boiling in extra amount of water), frying, and pressure cooking. The cooked rice was held at various temperatures and times as follows: it was made fresh (T1), kept at room temperature (20-22 °C) for 24 h (T2), kept at 4 °C for 24 h (T3), and then reheated after being kept at 4 °C for 24 h (T4). The proximate composition, total dietary fibre, resistant starch (RS), and in vitro starch digestion rate of products were examined. The effect of RS on blood glucose and lipid profiles was measured in humans and rats, including a histopathological study of the liver and pancreas in rats. The basmati rice that was prepared via boiling 1 and stored with T3 was found to be low in glycaemic index and glycaemic load, and to be high in resistant starch. Similarly, in rats, the blood glucose level, cholesterol, triglycerides, and LDL were reduced by about 29.7%, 37.9%, 31.3%, and 30.5%, respectively, after the consumption of basmati rice that was prepared via boiling 1 and stored with T3. Awareness should be raised among people about the health benefits of resistant starch consumption and the right way of cooking.
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The limited availability of molecularly targeted low-molecular-weight imaging agents for monitoring multiple myeloma (MM)-targeted therapies has been a significant challenge in the field. In response, a first-in-class peptide-based radiotracer, [68Ga]Ga-AJ206, is developed that can be seamlessly integrated into the standard clinical workflow and is specifically designed to noninvasively quantify CD38 levels and pharmacodynamics by positron emission tomography (PET). A bicyclic peptide, AJ206, is synthesized and exhibits high affinity to CD38 (KD: 19.1 ± 0.99 × 10-9 m) by surface plasmon resonance. Further, [68Ga]Ga-AJ206-PET shows high contrast within 60 min and suitable absorbed dose estimates for clinical use. Additionally, [68Ga]Ga-AJ206 detects CD38 expression in cell line-derived xenografts, patient-derived xenografts (PDXs), and disseminated disease models in a manner consistent with flow cytometry and immunohistochemistry findings. Moreover, [68Ga]Ga-AJ206-PET successfully quantifies CD38 pharmacodynamics in PDXs, revealing increased CD38 expression in the tumor following all-trans retinoic acid (ATRA) therapy. In conclusion, [68Ga]Ga-AJ206 exhibits the salient features required for clinical translation, providing CD38-specific high-contrast images in multiple models of MM. [68Ga]Ga-AJ206-PET could be useful for quantifying total CD38 levels and pharmacodynamics during therapy to evaluate approved and new therapies in MM and other diseases with CD38 involvement.
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ADP-Ribosil Ciclase 1 , Radioisótopos de Gálio , Mieloma Múltiplo , Tomografia por Emissão de Pósitrons , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/diagnóstico por imagem , Animais , ADP-Ribosil Ciclase 1/metabolismo , Camundongos , Humanos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Modelos Animais de Doenças , Peptídeos/metabolismo , Glicoproteínas de Membrana/metabolismo , Linhagem Celular TumoralRESUMO
Ethnomedicinal plants are a rich reservoir of active compounds with potent pharmacological properties. Therefore, plants could serve as a source for the discovery of active antimicrobial and antioxidant agents and are focused because of their low toxicity, economic viability, easy availability, etc. In this regard, phytochemical analyses, viz. ß-carotene, total sugar, reducing sugar, vitamin C, total carotenoids, protein, total phenolic content (TPC), and total flavonoid content (TFC) of 20 ethnomedicinal plants of North East India (NEI) were evaluated in this study. The antibacterial activity against human pathogens and antioxidant potential of plant extracts was also demonstrated. The minimum inhibitory concentration (MIC80), minimum bactericidal concentration (MBC), and total antibacterial activity (TAA) of the active extracts were evaluated against Pseudomonas aeruginosa and Chromobacterium violaceum. The active extracts were also examined for antibiofilm as well as anti-pyocyanin activities against P. aeruginosa and anti-QS activity against C. violaceum at sub-MICs. The study demonstrated variable concentration of phytochemicals of the extracts, viz. ß-carotene (0.29-8.91 mg g-1), total sugar (2.92-30.6 mM), reducing sugar (0.44-14.5 mM), vitamin C (8.41-31.3 mg g-1), total carotenoids (14.9-267.0 mg g-1), protein (5.65-283 mg g-1), TPC (5.32-31.0 mg GAE/g DW), and TFC (1.74-68.2 mg QE/g DW). The plant extracts also exhibited potent antioxidant and antibacterial activities against both Gram-positive and Gram-negative bacteria. Some of the extracts also demonstrated significant biofilm inhibition and eradication, anti-pyocyanin, and anti-QS activities at sub-MICs. The selected ethnomedicinal plants are rich in phytochemicals and demonstrated potent antioxidant, antibacterial, and antibiofilm activities, thus could serve as the important source of novel antioxidant and antimicrobial agents.
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Antibacterianos , Anti-Infecciosos , Humanos , Antibacterianos/química , Antioxidantes/farmacologia , Antioxidantes/análise , beta Caroteno , Bactérias , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Extratos Vegetais/química , Plantas , Anti-Infecciosos/farmacologia , Flavonoides/farmacologia , Flavonoides/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Fenóis/farmacologia , Biofilmes , Ácido Ascórbico , Açúcares , ÍndiaRESUMO
PURPOSE: Immune checkpoint therapy (ICT) is currently ineffective in a majority of patients. Tumor drug exposure measurements can provide vital insights into mechanisms involved in the resistance of solid tumors to those therapeutics; however, tools to quantify in situ drug exposure are few. We have investigated the potential of programmed death-ligand 1 (PD-L1) pharmacodynamics, quantified using PET, to inform on the tumor exposure of anti-PD-L1 (aPD-L1) therapeutics. EXPERIMENTAL DESIGN: To noninvasively quantify PD-L1 levels, we first developed a novel peptide-based gallium-68-labeled binder, [68Ga]Ga-DK223, and evaluated its in vivo distribution, pharmacokinetics, and PD-L1 specificity in preclinical models of triple-negative breast cancer and urothelial carcinoma with variable PD-L1 expression. We then quantified baseline and accessible PD-L1 levels in tumors as a noninvasive pharmacodynamic measure to assess tumor exposure to two aPD-L1 antibodies (avelumab and durvalumab). RESULTS: DK223 exhibited a KD of 1.01±0.83 nmol/L for PD-L1 and inhibited the PD-1:PD-L1 interaction in a dose-dependent manner. [68Ga]Ga-DK223 provides high-contrast PET images within 60 minutes of administration and detects PD-L1 in an expression-dependent manner in xenograft models. PD-L1 pharmacodynamics measured using [68Ga]Ga-DK223-PET revealed that avelumab and durvalumab had similar exposure early during therapy, but only durvalumab exhibited sustained exposure at the tumor. CONCLUSIONS: [68Ga]Ga-DK223 detected variable PD-L1 levels and exhibited salient features required for clinical translation. [68Ga]Ga-DK223-PET could be useful for quantifying total PD-L1 levels at baseline and accessible PD-L1 levels during therapy to understand drug exposure at the tumor, thus supporting its use for guiding and optimizing ICT.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Tomografia por Emissão de Pósitrons/métodos , Antígeno B7-H1/metabolismo , PeptídeosRESUMO
BACKGROUND: Combination therapies that aim to improve the clinical efficacy to immune checkpoint inhibitors have led to the need for non-invasive and early pharmacodynamic biomarkers. Positron emission tomography (PET) is a promising non-invasive approach to monitoring target dynamics, and programmed death-ligand 1 (PD-L1) expression is a central component in cancer immunotherapy strategies. [18F]DK222, a peptide-based PD-L1 imaging agent, was investigated in this study using humanized mouse models to explore the relationship between PD-L1 expression and therapy-induced changes in cancer. METHODS: Cell lines and xenografts derived from three non-small cell lung cancers (NSCLCs) and three urothelial carcinomas (UCs) were used to validate the specificity of [18F]DK222 for PD-L1. PET was used to quantify anti-programmed cell death protein-1 (PD-1) therapy-induced changes in PD-L1 expression in tumors with and without microsatellite instability (MSI) in humanized mice. Furthermore, [18F]DK222-PET was used to validate PD-L1 pharmacodynamics in the context of monotherapy and combination immunotherapy in humanized mice bearing A375 melanoma xenografts. PET measures of PD-L1 expression were used to establish a relationship between pathological and immunological changes. Lastly, spatial distribution analysis of [18F]DK222-PET was developed to assess the effects of different immunotherapy regimens on tumor heterogeneity. RESULTS: [18F]DK222-PET and biodistribution studies in mice with NSCLC and UC xenografts revealed high but variable tumor uptake at 60 min that correlated with PD-L1 expression. In MSI tumors treated with anti-PD-1, [18F]DK222 uptake was higher than in control tumors. Moreover, [18F]DK222 uptake was higher in A375 tumors treated with combination therapy compared with monotherapy, and negatively correlated with final tumor volumes. In addition, a higher number of PD-L1+ cells and higher CD8+-to-CD4+ cell ratio was observed with combination therapy compared with monotherapy, and positively correlated with PET. Furthermore, spatial distribution analysis showed higher [18F]DK222 uptake towards the core of the tumors in combination therapy, indicating a more robust and distinct pattern of immune cell infiltration. CONCLUSION: [18F]DK222-PET has potential as a non-invasive tool for monitoring the effects of immunotherapy on tumors. It was able to detect variable PD-L1 expression in tumors of different cancer types and quantify therapy-induced changes in tumors. Moreover, [18F]DK222-PET was able to differentiate the impact of different therapies on tumors.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Antígeno B7-H1 , Distribuição Tecidual , Tomografia por Emissão de Pósitrons/métodos , Imunoterapia/métodosRESUMO
PURPOSE: The limited availability of molecularly targeted low-molecular-weight imaging agents for monitoring multiple myeloma (MM)-targeted therapies has been a significant challenge in the field. In response, we developed [68Ga]Ga-AJ206, a peptide-based radiotracer that can be seamlessly integrated into the standard clinical workflow and is specifically designed to non-invasively quantify CD38 levels and pharmacodynamics by positron emission tomography (PET). EXPERIMENTAL DESIGN: We synthesized a high-affinity binder for quantification of CD38 levels. Affinity was tested using surface plasmon resonance, and In vitro specificity was evaluated using a gallium-68-labeled analog. Distribution, pharmacokinetics, and CD38 specificity of the radiotracer were assessed in MM cell lines and in primary patient-derived myeloma cells and xenografts (PDX) with cross-validation by flow cytometry and immunohistochemistry. Furthermore, we investigated the radiotracer's potential to quantify CD38 pharmacodynamics induced by all-trans retinoic acid therapy (ATRA). RESULTS: [68Ga]Ga-AJ206 exhibited high CD38 binding specificity (KD: 19.1±0.99 nM) and CD38-dependent In vitro binding. [68Ga]Ga-AJ206-PET showed high contrast within 60 minutes and suitable absorbed dose estimates for clinical use. Additionally, [68Ga]Ga-AJ206 detected CD38 expression in xenografts, PDXs and disseminated disease models in a manner consistent with flow cytometry and immunohistochemistry findings. Moreover, [68Ga]Ga-AJ206-PET successfully quantified CD38 pharmacodynamics in PDXs, revealing increased CD38 expression in the tumor following ATRA therapy. CONCLUSIONS: [68Ga]Ga-AJ206 exhibited the salient features required for clinical translation, providing CD38-specific high contrast images in multiple models of MM. [68Ga]Ga-AJ206-PET could be useful for quantifying total CD38 levels and pharmacodynamics during therapy to evaluate approved and new therapies in MM and other diseases with CD38 involvement.
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OIRD (opioid-induced respiratory depression) remains a significant public health concern due to clinically indicated and illicit opioid use. Respiratory depression is the sine qua non of opioid toxicity, and early detection is critical for reversal using pharmacologic and non-pharmacologic interventions. In addition to respiratory monitoring devices such as pulse oximetry, capnography, and contactless monitoring systems, novel implantable sensors and detection systems such as optical detection and electrochemical detection techniques are being developed to identify the presence of opioids both in vivo and within the environment. These new technologies will not only monitor for signs and symptoms of OIRD but also serve as a mechanism to alert and assist first responders and lay rescuers. The current opioid epidemic brings to the forefront the need for additional accessible means of detection and diagnosis. Rigorous evaluation of safety, efficacy, and acceptability will be necessary for both new and established technologies to have an impact on morbidity and mortality associated with opioid toxicity. Here, we summarized existing and advanced technologies for opioid detection and OIRD management with a focus on recent advancements in wearable and implantable opioid detection. We expect that this review will serve as a complete informative reference for the researchers and healthcare professionals working on the subject and allied fields.
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The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has severely impacted human health and the health management system globally. The ongoing pandemic has required the development of more effective diagnostic strategies for restricting deadly disease. For appropriate disease management, accurate and rapid screening and isolation of the affected population is an efficient means of containment and the decimation of the disease. Therefore, considerable efforts are being directed toward the development of rapid and robust diagnostic techniques for respiratory infections, including SARS-CoV-2. In this article, we have summarized the origin, transmission, and various diagnostic techniques utilized for the detection of the SARS-CoV-2 virus. These higher-end techniques can also detect the virus copy number in asymptomatic samples. Furthermore, emerging rapid, cost-effective, and point-of-care diagnostic devices capable of large-scale population screening for COVID-19 are discussed. Finally, some breakthrough developments based on spectroscopic diagnosis that could revolutionize the field of rapid diagnosis are discussed.
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The green synthesis of nanoparticles (NPs) is the safest, ecofriendly, cost-effective, and non-hazardous approach of nanotechnology. In the current study, we described the green synthesis of silver nanoparticles (AgNPs) using Cuphea carthagenensis aqueous leaf extract as a reducing, capping, and stabilizing agent. The study aims at the synthesis, characterization, optimization, and determination of the antibacterial activity of Cc-AgNPs against clinically important human pathogens. Coating of cotton fabrics with Cc-AgNPs and their efficacy against skin infection causing organisms was also evaluated. Furthermore, antioxidant activity, growth assay and time kill assay of Cc-AgNPs were also performed in the study. The biosynthesized Cc-AgNPs were characterized by UV-visible spectrometry, energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR). The spectroscopic and microscopic analysis demonstrated biosynthesis of face-centered cubic (fcc) crystalline spherical Cc-AgNPs with an average particle size of 10.65 ± 0.1 nm. Optimized peak synthesis of Cc-AgNPs was reported at pH7, 55 °C, 4 mM silver nitrate, and 5:45 (plant extract: silver nitrate). Cc-AgNPs exhibited potent antioxidant effect and antibacterial activity against both Gram-positive and Gram-negative bacteria. The lowest MIC (15 µg/ml) and MBC (25 µg/ml) values were reported against S. typhimurium. The Cc-AgNPs coated fabrics demonstrated potent antibacterial activity against tested strains. This application could be helpful in wound healing management. Furthermore, the hemolytic analysis demonstrated that Cc-AgNPs exhibit non-toxic nature against Red Blood Cells (RBCs) at the tested concentrations. In conclusion, the investigation demonstrated a fast, stable, and eco-friendly approach to the biosynthesis of Cc-AgNPs along with their antibacterial and antioxidant properties.
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Cuphea , Nanopartículas Metálicas , Antibacterianos/química , Antioxidantes/química , Antioxidantes/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Prata/farmacologia , Nitrato de Prata , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
The assembly of microorganisms over a surface and their ability to develop resistance against available antibiotics are major concerns of interest. To survive against harsh environmental conditions including known antibiotics, the microorganisms form a unique structure, referred to as biofilm. The mechanism of biofilm formation is triggered and regulated by quorum sensing, hostile environmental conditions, nutrient availability, hydrodynamic conditions, cell-to-cell communication, signaling cascades, and secondary messengers. Antibiotic resistance, escape of microbes from the body's immune system, recalcitrant infections, biofilm-associated deaths, and food spoilage are some of the problems associated with microbial biofilms which pose a threat to humans, veterinary, and food processing sectors. In this review, we focus in detail on biofilm formation, its architecture, composition, genes and signaling cascades involved, and multifold antibiotic resistance exhibited by microorganisms dwelling within biofilms. We also highlight different physical, chemical, and biological biofilm control strategies including those based on plant products. So, this review aims at providing researchers the knowledge regarding recent advances on the mechanisms involved in biofilm formation at the molecular level as well as the emergent method used to get rid of antibiotic-resistant and life-threatening biofilms.
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Antibacterianos , Fenômenos Fisiológicos Bacterianos , Biofilmes , Resistência Microbiana a Medicamentos , Percepção de Quorum , Antibacterianos/farmacologia , Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistência Microbiana a Medicamentos/genética , Percepção de Quorum/efeitos dos fármacosRESUMO
ETHNOPHARMCOLOGICAL RELEVANCE: Microbial biofilm formation, a quorum sensing (QS) regulated process, is one of the major causes of nosocomial and chronic infections, foodborne diseases, and associated deaths. Various approaches have been used to eradicate the menace of biofilm. Ethnomedicinal plants as potent antibiofilm agents are gaining a lot of interest in an era where the drug resistance is increasing and the availability of potent antibiotics is no longer promised. In this context, the methanol extract of Cuphea carthagenensis (CCMD), an ethno-medicinal and culinary herb, was evaluated as an antibiofilm and anti-QS agent against Pseudomonas aeruginosa. AIM OF THE STUDY: The aim of the study is to evaluate the antibiofilm and anti-QS activity of an ethnomedicinal plant against a strong biofilm forming microorganism, P. aeruginosa. METHODS: Antibiofilm activity of CCMD was demonstrated at different concentrations by Tissue Culture Plate, Test Tube method and other microscopic techniques. The effect of CCMD on QS and QS-related virulence factors viz. Pyocyanin, exopolymeric substance matrix (EPS), total protease, elastase, pyoverdin and swimming motility in P. aeruginosa were also evaluated. Antioxidant activity (DPPH & FRAP), total phenolic and flavonoid content were also checked. In order to determine the composition of the extract HPLC analysis was also performed. RESULTS: In vitro study demonstrated a significant inhibition of biofilm formation (81.88 ± 2.57%) as well as production of QS-dependent virulence factors in P. aeruginosa. The extract also inhibited violacein production (83.31 ± 2.77%) in Chromobacterium violaceum which correlates with the reduction in QS-mediated virulence factors. The extract showed 64.79% ± 0.83% DPPH scavenging activity and reduction of ferricyanide complex (Fe3+) to the ferrous form (Fe2+) in DPPH and FRAP assay, respectively. Furthermore, the extract showed thermal stability and does not have any growth inhibitory effect on P. aeruginosa. The HPLC analysis demonstrated the presence of ellagic acid, ascorbic acid and hippuric acid in the extract. CONCLUSION: This work is the first to demonstrate that C. carthagenensis can attenuate biofilm formation and QS-mediated virulence factors of P. aeruginosa. Further investigation is required to use this ethnomedicinal plant (CCMD) as an important source of antibiofilm agents.
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Antibacterianos/farmacologia , Cuphea/química , Medicina Tradicional/métodos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/fisiologia , Fatores de Virulência/antagonistas & inibidores , Antioxidantes/farmacologia , Ácido Ascórbico , Biofilmes/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Chromobacterium/efeitos dos fármacos , Ácido Elágico , Flavonoides/análise , Hipuratos , Indóis/antagonistas & inibidores , Fenóis/análise , Folhas de Planta/química , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Fatores de Virulência/metabolismoRESUMO
Aedes aegypti acts as a vector for several arboviral diseases that impose a major socio-economic burden. Moreover, the absence of a vaccine against these diseases and drug resistance in mosquitoes necessitates the development of new control strategies for vector-borne diseases. ABC transporters that play a vital role in immunity and other cellular processes in different organisms may act as non-canonical immune molecules against arboviruses, however, their role in mosquito immunity remains unexplored. This study comprehensively analyzed various genetic features of putative ABC transporters and classified them into A-H subfamilies based on their evolutionary relationships. Existing RNA-sequencing data analysis indicated higher expression of cytosolic ABC transporter genes (E & F Subfamily) throughout the mosquito development, while members of other subfamilies exhibited tissue and time-specific expression. Furthermore, comparative gene expression analysis from the microarray dataset of mosquito infected with dengue, yellow fever and West Nile viruses revealed 31 commonly expressed ABC transporters suggesting a potentially conserved transcriptomic signature of arboviral infection. Among these, only a few transporters of ABCA, ABCC and ABCF subfamily were upregulated, while most were downregulated. This indicates the possible involvement of ABC transporters in mosquito immunity.
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Tocotrienols (T3) are vitamin E components that inhibit 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), a primary target for cholesterol management. T3 was extracted from rice bran (RBE) using ultrasonic energy keeping solute: solvent ratio, power and time on specific energy and T3 concentration as responses as per Box-Behnken Design. The lowest specific energy (52.38 ± 0.14 J mL-1) uptake by the sample was most effective in enhancing the concentration of T3 in RBE (199.34 ± 0.63 µg mL-1). In vitro HMGR kinetics and in silico binding interactions of the identified α-, δ- and γ-T3 fractions were studied. Enzyme kinetic studies revealed an uncompetitive mode of inhibition by α-T3, γ-T3, and RBE and a mixed mode of inhibition for δ-T3. γ-T3 showed lowest IC50 concentration (11.33 µg mL-1) followed by α-T3 (16.73 µg mL-1), RBE (20.45 µg mL-1) and δ-T3 (23.16 µg mL-1). Molecular docking studies highlighted the hydrogen bonding of δ-T3 with Gln766 and α- and γ-T3 with Met655 and Val805 amino acid residues at the NADPH binding site of HMGR. Results indicate the potential use of T3 enriched RBE optimally extracted using ultrasound as potent HMGR inhibitor.
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Fibras na Dieta/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/química , Oryza/química , Tocotrienóis/química , Ultrassom , Sítios de Ligação , Colesterol , Cromatografia Líquida de Alta Pressão , Ácidos Graxos não Esterificados/química , Imageamento Tridimensional , Concentração Inibidora 50 , Cinética , Ligantes , Conformação Molecular , Simulação de Acoplamento Molecular , Oxirredutases , Peróxidos , Ligação Proteica , Solventes , Sonicação , Vitamina ERESUMO
Semi-synthetic analogs of pinitol were subjected to screening by determining TNF-alpha expression in human neutrophils using flowcytometry. Among the tested compounds, three derivatives displayed more than 50% inhibition of TNF-alpha cytokine secretion in LPS induced stimulated neutrophils and can be considered as potent anti-inflammatory moieties.