Bioactive Compounds To Combat The Pathogenic Microbes
The world is facing a serious threat in health care system due to the emergence of antibiotic resistant microorganisms, which makes several infections harder to treat. Use of antibiotics in animal husbandry (poultery, fishes), for the purpose of disease prevention or to promote growth, misuse of antibiotics in the treatment is one of are found as the major causes of, development of antibiotic resistant microorganisms. Once such a bacterial strain is generated, it may continually persist in environment and reachesanimals, fishes, birds and also extend to the human handlers (Levy et al. 1976). Whenever such microbes cause pathogenesis, the situation becomes more problematic due to their non-responsive nature against prevalent antibiotics. To confront this situation, extensive research has 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, considerable number of bioactive compounds need to be isolated and screened from either plant or microbial origin. Naturally derived products are much safer than synthetic drugs, because they are formed in organic systems, thus they are more compatible with human body. Synthetic products on the other hand, have noticeable side effects.
Among various natural sources, microorganisms represent a major dependable source for compelling bioactive compounds. Actinomycetes and fungi were found as more feasible used as major dependable screening sources, for the isolation and identification of pharmaceutically important compounds. Microbial derived compounds have enormous molecular diversity and biological functionality, which has brought attention to the endophytes, which are the microbes that inhabit inside a plant. Microbial products are also used as a template for synthesizing certain functional derivatives by modifying their basis structure, so that they become more effective than the parent compound. Compactin is produced by Penicillium brevicompactum. Penicillium citrinum have been used for the production of commercially important multifunctional derivatives like mevastatin, lovastatin, simvastatin etc. The use of natural products has been enormously successful in the discovery of new medicine, and endophytic fungi is found as a promising source for the origin of natural antimicrobials.
The probability to discover novel or exotic bioactive molecule from an endophytic fungus is greater than others. Broad spectrum antibacterial compound producing endophytic fungus. Penicillium setosum, was presciently isolated from Withania somnifera. Since the discovery of penicillin, Penicillium species haunted a conspicuous concern from other microbial groups. They are well-proven for their versatileness in the metabolic ability as well as their challenging nature affected by the production of certain physiologically noticeable compounds, like alkaloids, hormones, antibiotics, mycotoxins, etc. So far numerous pharmacologically important compounds have been reported from these species, moreover these are also remarked for the presence of certain mycotoxins like patulin, citrinin, ochratoxin etc. Prominently, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were reported for their alarming nosocomial effect, caused by their rapid multiplying action, as well as toxin secreting ability. They are also noticed for the sudden evolution on their antibiotic resistance mechanisms. Hence, disease transmission caused by harmful bacteria has become a big social problem. Conventional screening method, in search for a potential bioactive compound is tedious, time consuming, and cost intensive. Hence, an in-silico molecular docking approach is adopted to overlap the disadvantage of traditional methods. By using this method, less time is required for analyzing and identifying, the most prospective bioactive compound among mass array of compounds. Molecular Docking has been gaining much research attention during the natural product screening and drug development stages. This has been successfully applied in various ailment programmes rendering to predict the ligand (compound or drug candidate) receptor (e. g. proteins or nucleic acid involved in biological processes) interactions.
Bioactive compounds exert their antibacterial action against the pathogens through a complex process, starting from the physical interaction of a compound to its specific target, resulting in the alterations at the biochemical, molecular and ultrastructural level. The most probable binding site of the desired compound, to the encountered bacterium can be effectively interpreted using in-silico approach. Most important scrutinizing condition required for the in-silico study is the selection of appropriate targets related to the preferred ailment condition and identification of most suitable model from the protein data bank. According to the various mechanism of action prevalent antibiotic actions can be broadly classified as four ways (i) DNA gyrase inhibitors, (ii) Cell-wall synthesis inhibitors, (iii) Protein synthesis inhibitors and (iv) DNA-dependent RNA synthesis inhibitors.
Hence 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 present in the bioactive fraction with the aid of high resolution mass spectrometry. Furthermore, molecular docking studies against nine different targets with identified compounds were conducted.
