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Infusion or Decoction Extracts of Helianthus annuus Leaves: Potential Inhibitors for QS system and Biofilm Formation in Pseudomonas aeruginosa
Abstract
Pseudomonas aeruginosa is one of the drug-resistant opportunistic pathogens with the ability to form biofilm and to produce a number of virulence factors via Quorum Sensing (QS) regulation. Most researchers have focused on QS inhibition to overcome the drug resistance problem. QS inhibitor molecules are investigated from natural resources. In the present study, anti-QS activities of ethyl acetate extracts of decoction and infusion samples from Helianthus annuus leaves were tested on biosensor strains of P. aeruginosa (lasB-gfp, rhlA-gfp and pqsA-gfp), as well as anti-biofilm activities on PAO1 wild type. H. annuus leaf samples were firstly infused or decocted and then extracted with ethyl acetate. The efficacies of infusion or decoction extracts were examined at the concentrations of 240, 120, and 60 μg/ml in 96-well microplates and evaluated in Citation 3 multimode microplate reader (Biotek). The inhibition rates of decoction extracts were recorded as 70.61% for las, 44.09% for rhl and 83.77% pqs system at 240 μg/ml. The biofilm inhibition percentages of the extracts were determined to be 50.82% (±1.36). Moreover, inhibition rates for infusion extracts were detected as 62.08% for las, 45.15% for rhl and 77.79% for pqs, and 53.88% (±3.94) for biofilm formation. In conclusion, the potential efficacies of the extracts of decocted or infused H.annuus leaves were demonstrated on QS system and biofilm formation of P. aeruginosa. However, there is a need for more detailed investigations and determination of the active substances that have QSI and anti-biofilm effect.
The Asteraceae (formerly Compositae) family contains approximately 1600 genera, many of which are known for their phytochemistry and pharmacological properties. Helianthus annuus is one of the most important plants in this family, known for producing oil and playing an important role in the economies of countries. This plant’s traditional uses date back more than 3000 years. The plants are ethnomedicinally significant and contain a variety of alkaloids, terpenoids, carbohydrates, fixed oils, steroids, amino acids, and other compounds. An important point to emphasize in this book chapter is that plants are highly adaptable to various environmental conditions, making them easier to cultivate and yielding higher yields. There is a substantial literature on the plant, but as research-based knowledge grows, it must be updated, so we will attempt to update this plant’s information in terms of its traditional uses, phytochemistry, and pharmacology properties; the pharmacological properties of H. annuus were investigated using a variety of sources, including medicinal plant databases, ethnobotanical and ethnopharmacological books, and peer-reviewed papers. This book chapter delves deeply into the chemical, nutritional, and pharmacological properties of H. annuus.Keywords
Helianthus annuus
SunflowerAsteraceaeFatty acidsPhenolic acids
Seed oils from oleaginous plants are rich in fatty acids (FAs) that play important roles in the health of the consumers. Recent studies indicate that FA also can play an important role in communication and regulation of virulence in bacteria. Nevertheless, evidence demonstrating protection against bacterial infections mediated by their quorum sensing inhibition (QSI) activity is scarce. In this study, sunflower, chia, and amaranth oils, were assayed for their QSI capacity by inhibiting violacein production and alkaline exoprotease activity of Chromobacterium violaceum. In vitro assays revealed that the oils exhibited QSI activities, whereas in vivo they delayed death of mice inoculated intraperitoneally with the bacterium. Gas chromatography coupled with mass spectrometry analysis of the oils indicated the presence of saturated FA (SAFA) and unsaturated FA as main components. Through a structure-activity relationship study of free FAs, bactericidal effect was identified mainly for polyunsaturated FAs, whereas QSI activity was restricted to SAFA of chains 12-18 carbon atoms in length. These data correlate with a possible interaction suggested by molecular docking analysis of lauric, myristic, and stearic acids with the CviR protein. Our study highlights the antiquorum sensing potential of SAFA, which may be future antivirulence therapeutic agents for the treatment of bacterial infections.
The sunflower (Helianthus annuus L.) seed and sprout is a ubiquitous crop with abundant nutrients and biological activities. This review summarizes the nutritional and medical importance currently recognized but under-researched concerning both seed and sprout highlighting the potential benefits of their phytochemical constituents including phenolic acids, flavonoids and tocopherols. Furthermore, the dynamic metabolite changes which occur during germination and biological activities are evaluated. The aim is to provide scientific evidence for improving the dietary and pharmaceutical applications of this common but popular crop as a functional food.
This book focuses on the evolution of plant viruses, their molecular classification, epidemics and management, covering topics relating to evolutionary mechanisms, viral ecology and emergence, appropriate analysis methods, and the role of evolution in taxonomy. The currently emerging virus species are increasingly becoming a threat to our way of life, both economically and physically. Plant viruses are particularly significant as they affect our food supply and are capable of rapidly spreading to new plant species. In basic research, plant viruses have become useful models to analyze the molecular biology of plant gene regulation and cell-cell communication. The small size of DNA genome of viruses possesses minimal coding capacity and replicates in the host cell nucleus with the help of host plant cellular machinery. Thus, studying virus cellular processes provides a good basis for explaining DNA replication, transcription, mRNA processing, protein expression and gene silencing in plants. A better understanding of these cellular processes will help us design antiviral strategies for plants. The book provides in-depth information on plant virus gene interactions with hosts, localization and expression and the latest advances in our understanding of plant virus evolution, their responses and crop improvement. Combining characterization of plant viruses and disease management and presenting them together makes it easy to compare all aspects of resistance, tolerance and management strategies. As such, it is a useful resource for molecular biologists and plant virologists alike.
Bu calismada, Bilecik-Asagikoy, Bilecik-Pazaryeri-Buyuk Elmali, Bursa-Merkez, Edirne-Kesan-Kozkoy, Edirne-Kesan ve Edirne-Ipsala ilcelerinde ikamet eden ve arastirmaya gonullu olarak katilmayi kabul eden 263 birey ile yuz yuze anket yontemiyle gorusulmus ve hazirlanan anket formlarinda yer alan sorular yardimi ile arastirma icin gerekli bilgiler toplanmistir. Elde edilen bilgiler dogrultusunda, bitkilerin halk ilaci olarak kullanilan kisimlari, kullanilis amaclari ve hazirlanis sekilleri (dekoksiyon, infuzyon, lapa, merhem vb.) sorgulanarak kaydedilmistir. Toplanan bitki ornekleri bilimsel olarak tanimlanmis ve Hacettepe Universitesi Egitim Fakultesi Herbaryumu’nda (HEF) muhafaza edilmektedir. Calismada 33 familyaya ait 68 taksonun halk ilaci olarak kullanildigi tespit edilmistir. Bunlarin cogunlugunun Rosaceae (10 takson) , Lamiaceae (8 takson) , Asteraceae (7 takson) ve Poaceae (4 takson) familyalarina ait oldugu gorulmustur. Halk ilaci olarak kaydedilen 187 kullanim arasinda en fazla; gastro-intestinal sistem (46 kullanim; %24,6), solunum sistemi ve gogus hastaliklari (41 kullanim; %21,9), uriner sistem (18 kullanim; %9,6), hematopoetik, immun sistem ve kanser (18 kullanim; %9,6) yer almaktadir. Anahtar Kelimeler: Halk ilaci, Bilecik, Bursa, Edirne, Turkiye.
Helianthus annuus commonly known as “Sunflower” is a well-known plant in India and
Pakistan. It is native to North America. It is use in ethnomedicine for treating a number of
disease conditions which include heart disease, bronchial, laryngeal and pulmonary affections,
coughs and colds and in whooping cough. Helianthus annuus contains various bioactive
compounds which include phenol, terpene compounds, carbohydrates, flavanoids, tannins,
alkaloids, saponins, steroids, fixed oil and active proteins all of these contribute to its remedial
properties. H. annuus is pharmacologically studied for various activities including gantiinflammatory,
anti-oxidant, antitumor, antiasthmatic, antigen, antipyretic, astringent,
antihypoglycemic effect, antifungal activities, cathartic, diuretic, stimulant, vermifuge, vulneray
purposes and antimicrobial activities. The analysis of the phytochemical constituents, uses and
pharmacological properties of H. annuus was carried out by using different sources such as
medicinal plant databases, ethnobotanical and ethnopharmacological books and different
published papers. This review presents a reasonable study of the chemical; nutritional and
pharmacological properties of H. annuus
This paper aims to summarize the outcomes of in vivo and in vitro studies relating to cosmeceutical and phytopharmaceutical potency of sunflower seed oil based on the epidemiological evidence published in the last 13 years. Study design of the reviewed literature included 25 selected scientific articles, as follows: randomized human studies (11), animal studies (6), reviews (5), and in vitro studies (3). Topical applied product consisted in raw sunflower seed oil, mixtures with other oils or herbs, and trade cosmetic or medicinal products. Fatty acids from this vegetable oil were shown to alleviate symptoms associated with skin sensitivity and inflammatory skin disorders, as well as to protect skin from photodamage and photoaging. Health benefits of sunflower oil were also found when applying on gingival, respectively on gastric mucosa. In conclusion, topical administration has proven certain positive skin effects but further research may be warranted in order to design more potent and safe phytopharmaceuticals.
Pseudomonas aeruginosa causes severe and persistent infections in immune compromised individuals and cystic fibrosis sufferers. The infection is hard to eradicate as P. aeruginosa has developed strong resistance to most conventional antibiotics. The problem is further compounded by the ability of the pathogen to form biofilm matrix, which provides bacterial cells a protected environment withstanding various stresses including antibiotics. Quorum sensing (QS), a cell density-based intercellular communication system, which plays a key role in regulation of the bacterial virulence and biofilm formation, could be a promising target for developing new strategies against P. aeruginosa infection. The QS network of P. aeruginosa is organized in a multi-layered hierarchy consisting of at least four interconnected signaling mechanisms. Evidence is accumulating that the QS regulatory network not only responds to bacterial population changes but also could react to environmental stress cues. This plasticity should be taken into consideration during exploration and development of anti-QS therapeutics.
Despite recent scientific advancement and globalization, the system of traditional medicine and complementary/alternative medicine is considered as a primary health care modality in the resource-constrained health care settings. Herbal medicinal system has been postulated and established through empirical observation and trial and error experiments since time immemorial to maintain good health and alleviate ailments and diseases. Earlier, the importance of traditional medicinal plants and phytotherapy have often been disregarded and undervalued. Presently revitalization and renewed interest on traditional medicinal plants has been observed among the public and scientific community. However, several daunting challenges need to be flagged effectively and immediately for the promotion of traditional medicinal plants. The collaborative efforts of ethnobotanists, anthropologists, pharmacists, and physicians could be a workable strategy to evaluate and validate the usage of traditional medicinal plants with the modern scientific methods and innovative techniques. Furthermore, conducting clinical trials to assess their efficacy and human safety is imperative and inevitable.
SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.
The present review shows a listing of medicinal plants used in phytotherapy of diabetes and those experimentally studied as hypoglycaemic in Morocco. The review is presented as 3 tables. The first one includes the taxonomic classification of the plant, the popular names in Morocco, the parts used, the mode of preparation and the other medicinal uses and toxicity. The second table summarises the experiments done by Moroccan researchers to confirm the hypoglycemic activity of the medicinal plants. It also describes the methodology used, and the magnitude of the hypoglycemic activity. The third table lists the toxicological studies carried out with plants reported to be toxic. The large number of plants described in this review (94 species belonging to 38 families) demonstrated the prevalence of phytotherapy in Morocco. The plant families which contained the most commonly used species for their antidiabetic effects are: Compositae (18 species), Lamiaceae (14 sp.), Leguminosae (8 sp.), Liliaceae (5 sp.), Apiaceae (5 sp.), and Graminae (4 sp.). Among these medicinal plants, 17 are toxic, the most known being: Daphne gnidium, Nerium oleander, Ferula communis, Peganum harmala and Citrullus colocynthis.
An ethnobotanical survey was carried out in different regions of Iraq following interviews with various traditional healers, who are called Attars, and various other people. Ninety-seven medicinal plants belonging to forty-three families are listed in alphabetical order giving the parts used and method of preparation according to their therapeutic use.
Bacteria communicate through the production of diffusible signal molecules termed autoinducers. The molecules are produced at basal levels and accumulate during growth. Once a critical concentration has been reached, autoinducers can activate or repress a number of target genes. Because the control of gene expression by autoinducers is cell-density-dependent, this phenomenon has been called quorum sensing. Quorum sensing controls virulence gene expression in numerous micro-organisms. In some cases, this phenomenon has proven relevant for bacterial virulence in vivo. In this article, we provide a few examples to illustrate how quorum sensing can act to control bacterial virulence in a multitude of ways. Several classes of autoinducers have been described to date and we present examples of how each of the major types of autoinducer can be involved in bacterial virulence. As quorum sensing controls virulence, it has been considered an attractive target for the development of new therapeutic strategies. We discuss some of the new strategies to combat bacterial virulence based on the inhibition of bacterial quorum sensing systems.
Attenuation of Pseudomonas aeruginosa virulence by the use of small-molecule quorum-sensing inhibitors (referred to as the antipathogenic drug principle) is likely
to play a role in future treatment strategies for chronic infections. In this study, structure-based virtual screening was
used in a search for putative quorum-sensing inhibitors from a database comprising approved drugs and natural compounds. The
database was built from compounds which showed structural similarities to previously reported quorum-sensing inhibitors, the
ligand of the P. aeruginosa quorum-sensing receptor LasR, and a quorum-sensing receptor agonist. Six top-ranking compounds, all recognized drugs, were
identified and tested for quorum-sensing-inhibitory activity. Three compounds, salicylic acid, nifuroxazide, and chlorzoxazone,
showed significant inhibition of quorum-sensing-regulated gene expression and related phenotypes in a dose-dependent manner.
These results suggest that the identified compounds have the potential to be used as antipathogenic drugs. Furthermore, the
results indicate that structure-based virtual screening is an efficient tool in the search for novel compounds to combat bacterial
infections.
Novel molecular tools have been constructed which allow for in situ detection of N-acyl homoserine lactone (AHL)-mediated quorum sensing in Pseudomonas aeruginosa biofilms. The reporter responds to AHL activation of LasR by expression of an unstable version of the green-fluorescent protein (Gfp). Gfp-based reporter technology has been applied for non-destructive, single-cell-level detection of quorum sensing in laboratory-based P. aeruginosa biofilms. It is reported that a synthetic halogenated furanone compound, which is a derivative of the secondary metabolites produced by the Australian macroalga Delisea pulchra, is capable of interfering with AHL-mediated quorum sensing in P. aeruginosa. It is demonstrated that the furanone compound specifically represses expression of a PlasB-gfp reporter fusion without affecting growth or protein synthesis. In addition, it reduces the production of important virulence factors, indicating a general effect on target genes of the las quorum sensing circuit. The furanone was applied to P. aeruginosa biofilms established in biofilm flow chambers. The Gfp-based analysis reveals that the compound penetrates microcolonies and blocks cell signalling and quorum sensing in most biofilm cells. The compound did not affect initial attachment to the abiotic substratum. It does, however, affect the architecture of the biofilm and enhances the process of bacterial detachment, leading to a loss of bacterial biomass from the substratum.
Individuals with cystic fibrosis (CF) are commonly colonized with Pseudomonas aeruginosa. The chronic infections caused by P. aeruginosa are punctuated by acute exacerbations of the lung disease, which lead to significant morbidity and mortality. As regulators
of virulence determinants, P. aeruginosa quorum-sensing systems may be active in the chronic lung infections associated with CF. We have examined the levels of autoinducer
molecules and transcript accumulation from the bacterial populations found in the lungs of patients with CF. We detected biologically
active levels of N-(3-oxododecanoyl)-l-homoserine (3-oxo-C12-HSL) and N-butyryl-l-homoserine lactone (C4-HSL) in sputum from CF patients. Interestingly, it appears that C4-HSL is less frequently detected
than 3-oxo-C12-HSL in the lungs of patients with CF. We also examined the transcription of the autoinducer synthase gene lasI and showed that it is frequently expressed in the lungs of patients with CF. We observed a significant correlation between
the expression of lasI and four target genes of the Las quorum-sensing system. Taken together, our results indicate that quorum-sensing systems
are active and may control virulence factor expression in the lungs of patients with CF.
The Calgary Biofilm Device (CBD) was used to form bacterial biofilms of selected veterinary gram-negative and gram-positive pathogenic bacteria from cattle, sheep, pigs, chicken, and turkeys. The minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of ampicillin, ceftiofur, cloxacillin, oxytetracycline, penicillin G, streptomycin, tetracycline, enrofloxacin, erythromycin, gentamicin, tilmicosin, and trimethoprim-sulfadoxine for gram-positive and -negative bacteria were determined. Bacterial biofilms were readily formed on the CBD under selected conditions. The biofilms consisted of micro-colonies encased in extracellular polysaccharide material. Biofilms composed of Arcanobacterium (Actinomyces) pyogenes, Staphylococcus aureus, Staphylococcus hyicus, Streptococcus agalactiae, Corynebacterium renale, or Corynebacterium pseudotuberculosis were not killed by the antibiotics tested but as planktonic bacteria they were sensitive at low concentrations. Biofilm and planktonic Streptococcus dysgalactiae and Streptococcus suis were sensitive to penicillin, ceftiofur, cloxacillin, ampicillin, and oxytetracycline. Planktonic Escherichia coli were sensitive to enrofloxacin, gentamicin, oxytetracycline and trimethoprim/ sulfadoxine. Enrofloxacin and gentamicin were the most effective antibiotics against E. coli growing as a biofilm. Salmonella spp. and Pseudomonas aeruginosa isolates growing as planktonic populations were sensitive to enrofloxacin, gentamicin, ampicillin, oxytetracycline, and trimethoprim/sulfadoxine, but as a biofilm, these bacteria were only sensitive to enrofloxacin. Planktonic and biofilm Pasteurella multocida and Mannheimia haemolytica had similar antibiotic sensitivity profiles and were sensitive to most of the antibiotics tested. The CBD provides a valuable new technology that can be used to select antibiotics that are able to kill bacteria growing as biofilms.
Pseudomonas aeruginosa has two complete quorum-sensing systems. Both of these systems have been shown to be important for Pseudomonas virulence in multiple models of infection. Thus, these systems provide unique targets for novel antimicrobial drugs.
The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly tolerant to otherwise lethal doses of antibiotics, and protects against the bactericidal activity of polymorphonuclear leukocytes (PMNs). It has been previously demonstrated that QS is inhibited by garlic extract. In this study, the synergistic effects of garlic and tobramycin, and PMNs activities have been evaluated. P. aeruginosa was grown in vitro in continuous-culture once-through flow chambers with and without garlic extract. The garlic-treated biofilms were susceptible to both tobramycin and PMN grazing. Furthermore, the PMNs showed an increase in respiratory burst activation, when incubated with the garlic-treated biofilm. Garlic extract was administered as treatment for a mouse pulmonary infection model. Mice were treated with garlic extract or placebo for 7 days, with the initial 2 days being prophylactic before P. aeruginosa was instilled in the left lung of the mice. Bacteriology, mortality, histopathology and cytokine production were used as indicators. The garlic treatment initially provoked a higher degree of inflammation, and significantly improved clearing of the infecting bacteria. The results indicate that a QS-inhibitory extract of garlic renders P. aeruginosa sensitive to tobramycin, respiratory burst and phagocytosis by PMNs, as well as leading to an improved outcome of pulmonary infections.
An ethnobotanical survey was carried out on the territory of the highest mountain in Central Serbia, Kopaonik, which is characterized by great plant diversity. In total, 83 wild species from 41 families and 96 preparations for use in human therapy were recorded. Among those wild plants which are most commonly used for medicinal purposes, Hypericum perforatum L., Urtica dioica L., Achillea millefolium L., Matricaria chamomilla L., Sambucus nigra L., and Thymus serpyllum L. were particularly highly recommended by the majority of informants as being 'beneficial for all ailments'. The most frequently reported medicinal uses were for treating gastrointestinal ailments (50%), skin injuries and problems (25.6%), followed by respiratory, urinary-genital and cardiovascular problems (20.5%, 20.5%, 19.2%, respectively). Plants with unusual phytotherapeutic uses are Galium verum L. (sedative properties) and Eupatorium cannabinum L. (influenza-like illnesses), while plants with interesting but lesser-known properties include Daphne laureola L. (rheumatism and skin ailments) and Ficaria verna Huds. (tubers for treating haemorrhoids). In addition, 10 wild species used in veterinary medicine, as well as 25 herbs used for human nourishment were noted.
Extracellular DNA is one of the major matrix components in Pseudomonas aeruginosa biofilms. It functions as an intercellular connector and plays a role in stabilization of the biofilms. Evidence that DNA release in P. aeruginosa PAO1 biofilms is controlled by the las-rhl and pqs quorum-sensing systems has been previously presented. This paper provides evidence that DNA release in P. aeruginosa PAO1 biofilms is also under iron regulation. Experiments involving cultivation of P. aeruginosa in microtitre trays suggested that pqs expression, DNA release and biofilm formation were favoured in media with low iron concentrations (5 microM FeCl(3)), and decreased with increasing iron concentrations. Experiments involving cultivation of P. aeruginosa in a flow-chamber system suggested that a high level of iron (100 microM FeCl(3)) in the medium suppressed DNA release, structural biofilm development, and the development of subpopulations with increased tolerance toward antimicrobial compounds. Experiments with P. aeruginosa strains harbouring fluorescent reporters suggested that expression of the pqs operon was induced in particular subpopulations of the biofilm cells under low-iron conditions (1 microM FeCl(3)), but repressed in the biofilm cells under high-iron conditions (100 microM FeCl(3)).
The authoritative and comprehensive modern textbook on western herbal medicine - now in its second edition This long-awaited second edition of Principles and Practice of Phytotherapy covers all major aspects of herbal medicine from fundamental concepts, traditional use and scientific research through to safety, effective dosage and clinical applications. Written by herbal practitioners with active experience in clinical practice, education, manufacturing and research, the textbook is both practical and evidence based. The focus, always, is on the importance of tailoring the treatment to the individual case. New insights are given into the herbal management of approxiately 100 modern ailments, including some of the most challenging medical conditions, such as asthma, inflammatory bowel disease and other complex autoimmune and inflammatory conditions, and there is vibrant discussion around the contribution of phytotherapy in general to modern health issues, including health ageing. Fully referenced throughout, with more than 10, 000 citations, the book is a core resource for students and practitioners of phytotherapy and naturopathy and will be of value to all healthcare professionals - pharmacists, doctors, nurses - with an interest in herbal therapeutics.
Chromium fragments coordinated with graphene provide a potentially powerful method for the modification of graphene. The newly reported density functional theory method, M11-L, was employed to elucidate the coordination of chromium fragments with graphene. Oligoacenes were chosen to model graphene. The radii of the centrosymmetric oligoacenes were systematically increased to find the limit required to model graphene. meta-Trisubstituted benzene coordinated chromium fragments were employed to study the electronic effect of the complexation of chromium with graphene. The movement and arrangement of the chromium fragments on graphene is also studied.
The rapid evolution and dissemination of antibiotic resistance among bacterial pathogens are outpacing the development of new antibiotics, but antivirulence agents provide an alternative. These agents can circumvent antibiotic resistance by disarming pathogens of virulence factors that facilitate human disease while leaving bacterial growth pathways — the target of traditional antibiotics — intact. Either as stand-alone medications or together with antibiotics, these drugs are intended to treat bacterial infections in a largely pathogen-specific manner. Notably, development of antivirulence drugs requires an in-depth understanding of the roles that diverse virulence factors have in disease processes. In this Review, we outline the theory behind antivirulence strategies and provide examples of bacterial features that can be targeted by antivirulence approaches. Furthermore, we discuss the recent successes and failures of this paradigm, and new developments that are in the pipeline.
Microbial relationships with all life forms can be as free living, symbiotic or pathogenic. Human beings harbor 10 times more microbial cells than their own. Bacteria are found on the skin surface, in the gut and other body parts. Bacteria causing diseases are the most worrisome. Most of the infectious diseases are caused by bacterial pathogens with an ability to form biofilm. Bacteria within the biofilm are up to 1000 times more resistant to antibiotics. This has taken a more serious turn with the evolution of multiple drug resistant bacteria. Health Departments are making efforts to reduce high mortality and morbidity in man caused by them. Bacterial Quorum sensing (QS), a cell density dependent phenomenon is responsible for a wide range of expressions such as pathogenesis, biofilm formation, competence, sporulation, nitrogen fixation, etc. Majority of these organisms that are important for medical, agriculture, aquaculture, water treatment and remediation, archaeological departments are: Aeromonas, Acinetobacter, Bacillus, Clostridia, Enterococcus, Pseudomonas, Vibrio and Yersinia spp. Biosensors and models have been developed to detect QS systems. Strategies for inhibiting QS system through natural and synthetic compounds have been presented here. The biotechnological applications of QS inhibitors (QSIs) in diverse areas have also been dealt with. Although QSIs do not affect growth and are less likely to impose selective pressure on bacteria, however, a few reports have raised doubts on the fate of QSIs. This book addresses a few questions. Will bacteria develop mechanisms to evade QSIs? Are we watching yet another defeat at the hands of bacteria? Or will we be acting intelligently and survive the onslaughts of this Never Ending battle?.
Decades after the first patients were treated with antibiotics, bacterial infections have again become a threat because of the rapid emergence of resistant bacteria-a crisis attributed to abuse of these medications and a lack of new drug development.
The continued emergence of multi-drug-resistant bacteria is a major public health concern. The identification and development of new antibiotics, especially those with new modes of action, is imperative to help treat these infections. This review lists the 22 new antibiotics launched since 2000 and details the two first-in-class antibiotics, fidaxomicin (1) and bedaquiline (2), launched in 2011 and 2012, respectively. The development status, mode of action, spectra of activity, historical discovery and origin of the drug pharmacophore (natural product, natural product derived, synthetic or protein/mammalian peptide) of the 49 compounds and 6 β-lactamase/β-lactam combinations in active clinical development are discussed, as well as compounds that have been discontinued from clinical development since 2011. New antibacterial pharmacophore templates are also reviewed and analyzed.
Keywords:
antimicrobial resistance; antibiotic; clinical trials; drug development; drug discovery; natural product
Topical agents include anything that touches the infant's skin. The skin is crucial to the way the infant perceives and responds to the care environment and, therefore, in neurodevelopment. Psychological stress negatively affects the barrier. The full-term infant has well-developed epidermal barrier despite spending 9 months being submerged in water. Vernix caseosa is a natural topical agent that facilitates stratum corneum barrier development through protective and adaptive mechanisms. Its properties include hydration, wound healing, antiinfection, and acid mantle development. The ontogeny of neonatal skin development and vernix biology provide the basis for assisting barrier maturation in premature infants, treating compromised skin and selecting topical agents. The published research on the effects of topical products on premature and damaged neonatal skin is very limited, especially for adequately sized randomized controlled clinical trials. Health care providers have keen interest and the skills to identify improved treatments through outcomes-based research.
Pseudomonas aeruginosa uses a hierarchical quorum sensing (QS) network consisting of las, pqs and rhl regulatory elements to coordinate the expression of bacterial virulence genes. However, clinical isolates frequently contain loss-of-function mutations in the central las system. This motivated us to search for a mechanism that may functionally substitute las. Here we report identification of a new QS signal, IQS. Disruption of IQS biosynthesis paralyzes the pqs and rhl QS systems and attenuates bacterial virulence. Production of IQS is tightly controlled by las under normal culture conditions but is also activated by phosphate limitation, a common stressor that bacteria encounter during infections. Thus, these results have established an integrated QS system that connects the central las system and phosphate-stress response mechanism to the downstream pqs and rhl regulatory systems. Our discovery highlights the complexity of QS signaling systems and extends the gamut of QS and stress-response mechanisms.
Quorum sensing is a process of cell-cell communication that allows bacteria to share information about cell density and adjust gene expression accordingly. This process enables bacteria to express energetically expensive processes as a collective only when the impact of those processes on the environment or on a host will be maximized. Among the many traits controlled by quorum sensing is the expression of virulence factors by pathogenic bacteria. Here we review the quorum-sensing circuits of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Vibrio cholerae. We outline these canonical quorum-sensing mechanisms and how each uniquely controls virulence factor production. Additionally, we examine recent efforts to inhibit quorum sensing in these pathogens with the goal of designing novel antimicrobial therapeutics.
Plants have long been a source of therapeutic agents used by man. Some 80% of the world's population still rely upon plants for primary health care; even today in Western medicine, and despite progress in synthetic chemistry, some 25% of prescription medicines are still derived either directly or indirectly from plants. The use of plants in medicines ranges from crude preparations or extracts, to refined extracts and single molecular species. In terms of categories of use this encompasses food supplements, herbal medicines, botanical drugs and prescription medicines. Increased interest in plants as a source of novel pharmacophores recognizes their chemical diversity and versatility, not matched by synthetic chemistry libraries. In spite of the surge of activity in synthetic chemistry over the last 20 years or so, almost half the some 850 small molecules introduced as drugs were derived from plant sources. Over 100 small molecules derived either directly or indirectly from plants are currently at some point in the clinical trials process. It is argued that the present use of plant-derived drugs and remedies only scratches the surface of what is a major reservoir of untapped potential, the level of biological and chemical diversity possessed by plants having much to offer in the drive for novel therapeutic agents in the fight against disease. Additionally novel developments in plant biotechnology and molecular biology add further dimensions to the use of plants in the production of therapeutic agents. Copyright © 2006 Society of Chemical Industry
The Plants and Weeds are screened out for their antibacterial and antifungal activity against some gram-positive and gram-negative bacteria's by extracting out their aqueous and methanolic extracts and screened out by analyzing their zone of inhibition. The weed Dathura stromonium shows pronounced antibacterial and antifungal activity along with Azadirachta indica, when compared with some standard antibiotics.
Antibiotic resistance is one of the greatest challenges of the twenty-first century. However, the increasing understanding of bacterial pathogenesis and intercellular communication has revealed many potential strategies to develop novel drugs to treat bacteria-mediated disease. Interference with bacterial virulence and/or cell-to-cell signalling pathways is an especially compelling approach, as it is thought to apply less selective pressure for the development of bacterial resistance than traditional strategies, which are aimed at killing bacteria or preventing their growth. Here, we discuss the mechanisms of bacterial virulence and present promising anti-virulence strategies and compounds for the future treatment of bacterial infections.
Bacteria employ sophisticated cell-to-cell communication or 'quorum sensing' (QS) systems for promoting collective behaviours that depend on the actions of one or more chemically distinct diffusible signal molecules. As determinants of cell population density, multiple QS systems are often integrated with each other and within global regulatory networks and subject to the prevailing environmental conditions as well as the presence and activities of other organisms. QS signal molecules, although largely considered as effectors of QS-dependent gene expression are also emerging as multifunctional molecules that influence life, development and death in single and mixed microbial populations and impact significantly the outcome of host-pathogen interactions.
Acquired resistance to vancomycin is an increasing problem in pathogenic bacteria. It is best studied and most prevalent among Enterococcus and still remains rare in other pathogenic bacteria. Different genotypes of vancomycin resistance, vanA-G, have been described. The different van gene clusters consist of up to nine genes encoding proteins of different functions; their interplay leads to an alternative cell wall precursor less susceptible to glycopeptide binding. Variants of vanA and vanB types are found worldwide, with vanA predominating; their reservoir is Enterococcus faecium. Within this species a subpopulation of hospital-adapted types exists that acquired van gene clusters and which is responsible for outbreaks of vancomycin-resistant enterococci all over the world. Acquisition of vanA by methicillin-resistant Staphylococcus aureus (MRSA) is worrisome and seven cases have been described. Nonsusceptibility to glycopeptides also occurs independently from van genes and is a growing therapeutic challenge, especially in MRSA.
Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density. Quorum sensing bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density. The detection of a minimal threshold stimulatory concentration of an autoinducer leads to an alteration in gene expression. Gram-positive and Gram-negative bacteria use quorum sensing communication circuits to regulate a diverse array of physiological activities. These processes include symbiosis, virulence, competence, conjugation, antibiotic production, motility, sporulation, and biofilm formation. In general, Gram-negative bacteria use acylated homoserine lactones as autoinducers, and Gram-positive bacteria use processed oligo-peptides to communicate. Recent advances in the field indicate that cell-cell communication via autoinducers occurs both within and between bacterial species. Furthermore, there is mounting data suggesting that bacterial autoinducers elicit specific responses from host organisms. Although the nature of the chemical signals, the signal relay mechanisms, and the target genes controlled by bacterial quorum sensing systems differ, in every case the ability to communicate with one another allows bacteria to coordinate the gene expression, and therefore the behavior, of the entire community. Presumably, this process bestows upon bacteria some of the qualities of higher organisms. The evolution of quorum sensing systems in bacteria could, therefore, have been one of the early steps in the development of multicellularity.
Pseudomonas aeruginosa is an important bacterial pathogen, particularly as a cause of infections in hospitalised patients, immunocompromised hosts and patients with cystic fibrosis. Surveillance of nosocomial P. aeruginosa infections has revealed trends of increasing antimicrobial resistance, including carbapenem resistance and multidrug resistance. Mechanisms of antimicrobial resistance include multidrug efflux pumps, ss-lactamases and downregulation of outer membrane porins. Mechanisms of virulence include secreted toxins and the ability to form biofilms. The effective treatment of infections caused by P. aeruginosa includes prevention when possible, source control measures as necessary and prompt administration of appropriate antibacterial agents. Antibacterial de-escalation should be pursued in patients with an appropriate clinical response, especially when antibacterial susceptibilities are known. Multidrug-resistant P. aeruginosa may require treatment with less commonly used antibacterials (e.g. colistin), but newer anti-pseudomonal antibacterials are expected to be available in the near future.
Bitkilerden elde edilen anti quorum sensing bileşikleri ve yeni ilaç geliştirmedeki potansiyelleri
- E Cepni
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Principles and practice of phytotherapy modern herbal medicine: Dosage and dosage forms in herbal medicine
- K Bone
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Anti-virulence strategies to combat bacteria-mediated disease
- D A Rasko
- V Sperandio