Resurgence of the Interest in Microorganisms and Plants as Sources of Secondary Metabolites for Treating Staphylococcal Infections

2019 ◽  
Vol 9 (1) ◽  
pp. 14-25 ◽  
Author(s):  
Mária Mikulášová
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Plant Extracts ◽  
Antibiotic Resistant ◽  
Staphylococcal Infections ◽  
Biological Methods ◽  
Antibiotic Discovery ◽  
Uncultured Microorganisms ◽  
Virulence Factor Production ◽  
New Strategies

Background: The golden era of antibiotic discovery from Actinomycetes peaked in the middle of the 20th century and then got abandoned. Efforts to do a screening of synthetic compounds libraries and rational target-based drug design were not successful and only a few new classes of antibiotics have been described over the past 60 years. </P><P> Objective: This review summarizes the newest knowledge about two untapped sources of antibacterial natural products - microorganisms and plants. Methods: Research and review papers of the last decades were analyzed and the data were summarizes to present the potential sources and mechanisms of natural products, which have the potential to cope with staphylococcal infections. Results: By using modern molecular biological methods, metagenomics and sequencing, it was found out that Actinomycetes harbor many more operons coding for secondary metabolites with antimicrobial potential than we can account for. Methods to grow uncultured microorganisms have been developed and the uncultured microorganisms show promising potential for new antimicrobials. The inhibition of pathogenicity of microorganisms via Quorum sensing inhibition, inhibition of virulence factor production or biofilm formation by plant extracts offers new ways to control antibiotic- resistant pathogens. Plant extracts with resistance modifying activity, e.g. efflux pumps inhibitors used as antibiotic adjuvants have the potential to restore the therapeutic activity of drugs. Conclusion: The findings from this review article confirm that new strategies, based on secondary metabolites of Actinomycetes, uncultured microorganisms and plants may open new ways to overcome the post-antibiotic era.

Something old, something new: revisiting natural products in antibiotic drug discovery

2014 ◽  
Vol 60 (3) ◽  
pp. 147-154 ◽  
Author(s):  
Gerard D. Wright
Keyword(s):  
Natural Products ◽  
New Drugs ◽  
Clinical Use ◽  
Antibiotic Resistant ◽  
Antibiotic Drug ◽  
New Antibiotics ◽  
Bacteria And Fungi ◽  
Antibiotic Discovery ◽  
Novel Drug ◽  
New Strategies

Antibiotic discovery is in crisis. Despite a growing need for new drugs resulting from the increasing number of multi-antibiotic-resistant pathogens, there have been only a handful of new antibiotics approved for clinical use in the past 2 decades. Faced with scientific, economic, and regulatory challenges, the pharmaceutical sector seems unable to respond to what has been called an “apocalyptic” threat. Natural products produced by bacteria and fungi are genetically encoded products of natural selection that have been the mainstay sources of the antibiotics in current clinical use. The pharmaceutical industry has largely abandoned these compounds in favor of large libraries of synthetic molecules because of difficulties in identifying new natural product antibiotics scaffolds. Advances in next-generation genome sequencing, bioinformatics, and analytical chemistry are combining to overcome barriers to natural products. Coupled with new strategies in antibiotic discovery, including inhibition of resistance, novel drug combinations, and new targets, natural products are poised for a renaissance to address what is a pressing health care crisis.

scholarly journals Review on the Antibacterial Mechanism of Plant-Derived Compounds against Multidrug-Resistant Bacteria (MDR)

2021 ◽  
Vol 2021 ◽  
pp. 1-30
Author(s):  
Najwan Jubair ◽  
Mogana Rajagopal ◽  
Sasikala Chinnappan ◽  
Norhayati Binti Abdullah ◽  
Ayesha Fatima
Keyword(s):  
Secondary Metabolites ◽  
Plant Secondary Metabolites ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Resistance Strategies ◽  
Microbial Infections ◽  
Ancient Times ◽  
Antibiotic Discovery

Microbial resistance has progressed rapidly and is becoming the leading cause of death globally. The spread of antibiotic-resistant microorganisms has been a significant threat to the successful therapy against microbial infections. Scientists have become more concerned about the possibility of a return to the pre-antibiotic era. Thus, searching for alternatives to fight microorganisms has become a necessity. Some bacteria are naturally resistant to antibiotics, while others acquire resistance mainly by the misuse of antibiotics and the emergence of new resistant variants through mutation. Since ancient times, plants represent the leading source of drugs and alternative medicine for fighting against diseases. Plants are rich sources of valuable secondary metabolites, such as alkaloids, quinones, tannins, terpenoids, flavonoids, and polyphenols. Many studies focus on plant secondary metabolites as a potential source for antibiotic discovery. They have the required structural properties and can act by different mechanisms. This review analyses the antibiotic resistance strategies produced by multidrug-resistant bacteria and explores the phytochemicals from different classes with documented antimicrobial action against resistant bacteria, either alone or in combination with traditional antibiotics.

scholarly journals Natural products and their derived compounds inhibitors of the enzyme acetylcholinesterase

2020 ◽  
pp. 149-160
Author(s):  
Maha Z. Rizk ◽  
Hanan F. Aly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Secondary Metabolites ◽  
Plant Extracts ◽  
Elderly Population ◽  
Acetylcholinesterase Inhibitors ◽  
The Elderly ◽  
Neurodegenerative Pathology ◽  
The Brain

Alzheimer’s disease (AD) is a progressive, neurodegenerative pathology that primarily affects the elderly population, and is estimated to account for 50-60% of dementia cases in persons over 65 years of age. The main characteristics connected with AD implicate the dysfunction of cognitive role, mainly loss of memory. While, the main features linked with AD at later stages include deficits of language, depression and problems associated with behavior. One of the most important approaches for medication of this disease is to improve level of the acetylcholine in the brain tissues using inhibitors of acetylcholinesterase (AChE). The present work reviews the literature on natural products from plants and plant-derived compounds inhibitors of enzyme acetylcholinesterase. Keywords: Alzheimer’s disease; Acetylcholinesterase inhibitors; Secondary metabolites; Plant extracts; essential oils

Molecular Docking Approaches to Suggest the Anti-Mycobacterial Targets of Natural Products

2020 ◽  
Author(s):  
Rafael Baptista ◽  
Sumana Bhowmick ◽  
Shen Jianying ◽  
Luis Mur
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Free Energies ◽  
Antibiotic Resistant ◽  
Drug Lead ◽  
Bisbenzylisoquinoline Alkaloids ◽  
Docking Approach ◽  
Global Threat ◽  
Physicochemical And Structural Properties

Tuberculosis (TB) is a major global threat mostly due to the development of antibiotic resistant forms of Mycobacterium tuberculosis, the causal agent of the disease. Driven by the pressing need for new anti-mycobacterial agents, several natural products (NPs) have been shown to have in vitro activities against M. tuberculosis. The utility of any NP as a drug lead is augmented when the anti-mycobacterial target(s) is unknown. To suggest these, we used a molecular docking approach to predict the interactions of 53 selected anti-mycobacterial NPs against known ‘druggable’ mycobacterial targets ClpP1P2, DprE1, InhA, KasA, PanK, PknB and Pks13. The docking scores / binding free energies were predicted and calculated using AutoDock Vina along with physicochemical and structural properties of the NPs, using PaDEL descriptors. These were compared to the established inhibitor (control) drugs for each mycobacterial target. The specific interactions of the bisbenzylisoquinoline alkaloids 2-nortiliacorinine, tiliacorine and 13’-bromotiliacorinine against the targets PknB and DprE1 (-11.4, -10.9 and -9.8 kcal.mol-1 ; -12.7, -10.9 and -10.3 kcal.mol-1 , respectively) and the lignan αcubebin and Pks13 (-11.0 kcal.mol-1 ) had significantly superior docking scores compared to controls. Our approach can be used to suggest predicted targets for the NP to be validated experimentally but these in silico steps are likely to facilitate drug optimisation.

In vitro antibacterial and antibiotic-potentiation activities of five edible plant extracts and mode of action against several MDR Gram-negative phenotypes

2020 ◽  
Vol 4 (1) ◽  
pp. 1-14
Author(s):  
Carine M.N. Ngaffo ◽  
Simplice B. Tankeo ◽  
Michel-Gael F. Guefack ◽  
Brice E. N. Wamba ◽  
Paul Nayim ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Bioactive Compounds ◽  
Plant Extracts ◽  
Theobroma Cacao ◽  
Efflux Pumps ◽  
Phoenix Dactylifera ◽  
Food Plants ◽  
Proton Pumps ◽  
Gram Negative ◽  
E Coli

Abstract Background: Bacterial infections involving the multidrug resistant (MDR) strains are among the top leading causes of death throughout the world. Healthcare system across the globe has been suffering from an extra-ordinary burden in terms of looking for the new and more potent antimicrobial compounds. The aim of the present study was to determine the antibacterial activity of some Cameroonian edible plants (Garcinia lucida bark, Phoenix dactylifera pericarps, Theobroma cacao pod, Solanum macrocarpon leaves and Termitomyces titanicus whole plant) and their antibiotics-potentiation effects against some MDR Gram-negative bacteria phenotypes expressing efflux pumps (Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa and Providencia stuartii strains). Methods: The antibacterial activities of plant extract alone and in combination with usual antibiotics were carried out using the micro-dilution method. The effects of the most active plant extract (Garcinia lucida bark) on H+-ATPase-mediated proton pumps and on bacterial growth kinetic were performed using experimental protocols, while qualitative reference methods were used to highligh the major groups of secondary metabolites present in the extracts. Results: Qualitative phytochemical screening of plant extracts indicated that all analysed secondary metabolites were present in Theobroma cacao and Termitomyces titanicus while one (saponins) of them was absent in Garcinia lucida and Solanum macrocarpon. Only three of them (polyphenols, flavonoids and saponins) were detected in Phoenix dactylifera. Antibacterial essays showed that G. lucida was the most active plant as it inhibited the growth of all studied bacteria with strong activity (MIC<100 µg/mL) against E. coli ATCC8739, significant activity (100≤MIC≤512 µg/mL) against 80% of bacteria and moderate activity (512<MIC≤2048 µg/mL) against E. coli AG100A and E. aerogenes (EA289 and CM64). It was followed by T. cacao and S. macrocarpon extracts which exhibited an antibacterial potential against 95% and 80% of bacterial strains, respectively. These three extracts exhibited a bactericidal effect on a few bacteria. Extracts from T. titanicus and P. dactylifera were less active as they moderately (512<MIC≤2048 µg/mL) inhibited the growth of 35% and 10% of bacteria. All extracts selectively potentiated the activities of all antibiotics with improvement activity factors (IAF) ranging from 2 to 256. G. lucida, T. cacao and S. macrocarpon potentiated the activities of 100%, 89% and 67% of antibiotics respectively against more than 70%, suggesting that they contain bioactive compounds which could be considered as efflux pumps inhibitors. Whereas T. titanicus and P. dactylifera improved the activities of almost 40% and 20% of antibiotics, respectively. This increase of activities also characterizes synergistic effects between antibiotics and these bioactive compounds. G. lucida extract at all tested concentrations, strongly inhibited the growth of bacterial strain E. coli ATCC8739 and exhibited an inhibitory effect on this bacterial H+-ATPase-mediated proton pumps increasing the pH of the medium. Conclusion: The overall results indicated that food plants among which G. lucida, T. cacao and S. macrocarpon could have a benefit interest in combatting resistant types of bacteria. Keywords: Food plants; infectious diseases; MDR bacteria; efflux pumps; antibiotics; secondary metabolites.

Plant Extracts and their Secondary Metabolites as Modulators of Kinases

2020 ◽  
Vol 20 (12) ◽  
pp. 1093-1104 ◽  
Author(s):  
Muhammad Shoaib Ali Gill ◽  
Hammad Saleem ◽  
Nafees Ahemad
Keyword(s):  
Signal Transduction ◽  
Secondary Metabolites ◽  
Plant Extracts ◽  
Cell Biology ◽  
Kinase Inhibitor ◽  
Plant Secondary Metabolites ◽  
Biological Properties ◽  
Drug Candidate ◽  
New Chemical Entities ◽  
Natural Flora

Natural Products (NP), specifically from medicinal plants or herbs, have been extensively utilized to analyze the fundamental mechanisms of ultimate natural sciences as well as therapeutics. Isolation of secondary metabolites from these sources and their respective biological properties, along with their lower toxicities and cost-effectiveness, make them a significant research focus for drug discovery. In recent times, there has been a considerable focus on isolating new chemical entities from natural flora to meet the immense demand for kinase modulators, and also to overcome major unmet medical challenges in relation to signal transduction pathways. The signal transduction systems are amongst the foremost pathways involved in the maintenance of life and protein kinases play an imperative part in these signaling pathways. It is important to find a kinase inhibitor, as it can be used not only to study cell biology but can also be used as a drug candidate for cancer and metabolic disorders. A number of plant extracts and their isolated secondary metabolites such as flavonoids, phenolics, terpenoids, and alkaloids have exhibited activities against various kinases. In the current review, we have presented a brief overview of some important classes of plant secondary metabolites as kinase modulators. Moreover, a number of phytocompounds with kinase inhibition potential, isolated from different plant species, are also discussed.

scholarly journals Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 107
Author(s):  
Rafael de Felício ◽  
Patricia Ballone ◽  
Cristina Freitas Bazzano ◽  
Luiz F. G. Alves ◽  
Renata Sigrist ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Deep Sea ◽  
Chemical Space ◽  
Bacterial Genome ◽  
Vast Number ◽  
Bacterial Metabolites ◽  
Laboratory Conditions ◽  
Deep Sea Bacteria

Bacterial genome sequencing has revealed a vast number of novel biosynthetic gene clusters (BGC) with potential to produce bioactive natural products. However, the biosynthesis of secondary metabolites by bacteria is often silenced under laboratory conditions, limiting the controlled expression of natural products. Here we describe an integrated methodology for the construction and screening of an elicited and pre-fractionated library of marine bacteria. In this pilot study, chemical elicitors were evaluated to mimic the natural environment and to induce the expression of cryptic BGCs in deep-sea bacteria. By integrating high-resolution untargeted metabolomics with cheminformatics analyses, it was possible to visualize, mine, identify and map the chemical and biological space of the elicited bacterial metabolites. The results show that elicited bacterial metabolites correspond to ~45% of the compounds produced under laboratory conditions. In addition, the elicited chemical space is novel (~70% of the elicited compounds) or concentrated in the chemical space of drugs. Fractionation of the crude extracts further evidenced minor compounds (~90% of the collection) and the detection of biological activity. This pilot work pinpoints strategies for constructing and evaluating chemically diverse bacterial natural product libraries towards the identification of novel bacterial metabolites in natural product-based drug discovery pipelines.

scholarly journals Crocus sativus L. Extract and Its Constituents: Chemistry, Pharmacology and Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4226
Author(s):  
Nikolaos Pitsikas ◽  
Konstantinos Dimas
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Organic Compounds ◽  
Therapeutic Potential ◽  
Crocus Sativus ◽  
Natural Sources ◽  
Crocus Sativus L

Natural products or organic compounds isolated from natural sources as primary or secondary metabolites have inspired numerous drugs [...]

scholarly journals MeFSAT: a curated natural product database specific to secondary metabolites of medicinal fungi

RSC Advances ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 2596-2607
Author(s):  
R. P. Vivek-Ananth ◽  
Ajaya Kumar Sahoo ◽  
Kavyaa Kumaravel ◽  
Karthikeyan Mohanraj ◽  
Areejit Samal
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Chemical Space ◽  
Therapeutic Uses ◽  
Medicinal Fungi ◽  
Fungal Natural Products

First dedicated manually curated resource on secondary metabolites and therapeutic uses of medicinal fungi. Cheminformatics based analysis of the chemical space of fungal natural products.

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