Natural Sources As Novel Drugs To Combat The Pathogenic Microbes
The world is facing a serious threat in health care system due to the emergence of antibiotic resistance microorganisms, which makes several infections harder to treat. Tremendously increasing in the number of antibiotic resistant microorganisms in different field like poultry, agriculture, homecare, and aquaculture. Once the resistant bacterial strain emerges, it may persist in animal, fishes, birds and simultaneously reaches to the human handlers. Whenever it causes the pathogenesis, situation become more problematic by their non-responsive nature against current drugs. To confront this situation, extensive researches have been taking place all over the world for the development of novel drugs or mechanisms of action to combat the pathogenic microbes. In this regard, infinite quantity of bioactive compounds have obtained only from a living organisms can be termed as natural products.
Amongst various natural sources microorganisms represent a major source of approved drugs and still play an important role in supplying chemical diversity. Majorly actinomycetes and fungi have used a major dependable screening source for the isolation and identification of pharmaceutically important bioactive compounds. Naturally isolating compounds have enormous molecular diversity and biological functionality, so this have gain more attention for the continual exploration compounds is an essential concern at present. Many researches are being conducted for the development of potent biosynthetic compounds by exploiting naturally derived compounds as a template for the modification.
Compactin, whichich is produced Penicillium brevicompactum, Penicillium citrinum have been biosynthetically modified, leads to the emergence of commercially important multifunctional derivatives like mevastatin, lovastatin simvastatin etc have great commercially importance, primarily it was reported to be produced by Natural compounds or their biosynthetic derivatives attain more attention than alternative synthetics drug discovery method, because which is extremely difficult to succeed in each stage of synthesis along with their noticeable side effects. The use of natural products has been enormously successful in the discovery of new medicine, and endophytic fungi could be a source of natural antimicrobials.
Despite Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) have seriously threatened to human health due to rapid proliferation and secretion of toxins or other metabolites. Hence, disease transmission caused by harmful bacteria has become a big social problem. Focusing on endophytic fungus isolated from a well-reputed medicinal plant serve as a successful area in search for natural antimicrobial.
Discovery of new bioactive molecules can occur in unexpected microbial taxa. The potential for discovery of new secondary metabolites with beneficial use for humans is great. To overlap the disadvantages of the available antimicrobial drugs, more antibiotics are needed to combat evolving pathogens, naturally resistant microbes, and bacteria and fungi that have developed resistance to current antibiotics. Many endophytic Penicillium species have been reported for the production some versatile bioactive compounds. So far numerous pharmacologically important compounds have been discovered from these species. Many human diseases can be cured by certain compounds extracted from natural sources. Moreover, isolating bioactive compounds from endophytes have attracted much attention. Of the 12, 000 antibiotics known in 1955, filamentous fungi produced 22 %. Microscopic fungi of the genus Penicillium are one of the most promising sources of physiologically active compounds, including alkaloids, antibiotics, hormones, mycotoxins, etc. Many of the plant origin compounds have been found to be endophytic fungal metabolite Flavonoids are the most common and widely distributed group of plant phenolic compounds, found in almost all plant parts, particularly in the photosynthesizing plant cells.
Plant flavonoids represent an important group of secondary metabolites. They are polyphenolic compounds that are found in almost all plant species. Extensive biological roles of flavonoids have been reported which include antiviral, anti-hepatotoxic, therapeutic, antibacterial, and other roles in nature. Plant flavonoids are generally found in low, variable concentrations and hence, it is challenging to find their consistent supply. Therefore, numerous biotechnological approaches have been explored for the enhanced production of these biologically and pharmacologically beneficial compounds.
Antibiotic-mediated cell death, however, is a complex process that begins with the physical interaction between a drug molecule and its bacterial-specific target, and involves alterations to the affected bacterium at the biochemical, molecular and ultrastructural levels. Antibiotic actions can be broadly classified as four ways (1) DNA gyrase inhibitors, (2) cell-wall synthesis inhibitors, (3) protein synthesis inhibitors and (4) DNA-dependent RNA synthesis inhibitors. Different approaches can be implemented to increase the probability of finding new bioactive molecules of accessing unexplored microorganisms. Molecular docking is an in silico tool that predicts how a ligand (substrate or drug candidate) interacts with a receptor (e. g. proteins involved in several biological processes) and has been successfully applied in several therapeutic programmes at the lead discovery stage.
In a previous study, we isolated the endophytic fungus P. setosum from Withania somnifera and found it to have potent antibacterial activity against both Gram-positive and Gram-negative bacteria. So this study was aimed to evaluate the antibacterial action of P. setosum metabolites against E. coli and S. aureus with respect to their morphological and intercellular changes. Then identify the responsible antibacterial constituents from the bioactive fraction with the aid of high resolution mass spectrometry. Furthermore molecular docking studies against nine different targets with identified compounds were conducted.
