Lantibiotics as Alternative Therapeutics

Description

Lantibiotics as Alternative Therapeutics explores alternative therapeutics, lantibiotics and other novel drugs. This book provides concrete information to readers regarding lantibiotics and various types of antimicrobial peptides with their mode of actions in treating various multidrug resistant organisms. It explains various techniques that are involved in analyzing antimicrobial peptides and their mode of actions. The development of antibiotic resistance has now reached a point of crisis where innovative methods and application of novel compounds and methods are required to prevent the spread of drug resistant infections. Novel compounds exhibit different modes of action to the currently used mechanism of therapeutics in order to combat against the resistant organisms. Lantibiotics hold considerable potential as a consequence of their unusual structure, unique mechanisms of action and their potency against multi-drug resistant bacteria. This book will be useful for pharmaceutical industry scientists and researchers in microbial and biomedical research as well as graduate and advanced students in microbiology, medical biotechnology, health, and pharmaceutical sciences. Front Cover Lantibiotics as Alternative Therapeutics Copyright Page Contents List of contributors Preface 1 Quandary of antibiotics and multidrug resistance development: a molecular genetics-based dilemma Introduction Brief history on assortment of antibiotics Classification based on origin of antibiotics Classification concerning the response for parasitic cells Classification based on molecular mechanisms of antibiotics against the pathogen Beta-lactams and its mode of action in molecular level Aminoglycosides and tetracyclines including mode of action in molecular level Macrolides and its mode of action in molecular level Quinolones and its mode of action in molecular level Sulfonamides and its mode of action in molecular level General synopsis on antibiotic resistance and multidrug resistance phenomena Molecular mechanism of antibiotic resistance and multidrug resistance phenomena Impact of microbial genetics, microbial physiology, and stress factors on antibiotic and/or multidrug resistance Technologies to address antibiotic resistance and/or multidrug resistance Conclusion References 2 Antimicrobial peptides and their potent mechanism of action Introduction Bacterial antimicrobial peptides with potent antibacterial activity Classification of bacteriocin Secondary structure Less common class of antimicrobial peptides Amino acid composition Mode of action of bacteriocin Other applications of bacteriocin Important steps in development of bacteriocins Preclinical studies of bacteriocins Toxicity of bacteriocins Challenges in using bacteriocins as therapeutic paradigm Future directions Conclusion References Further reading 3 Biosynthesis of lantibiotics Introduction Types of lantibiotics Gene arrangement Biosynthesis of lantibiotics Precursor peptides of lantibiotics The LanB enzyme The LanC enzyme The LanM enzyme The LanD enzyme Other posttranslational modifications Proteases and transporters Regulation of lantibiotic biosynthesis Autoregulation of nisin production Regulation of lacticin 3147 immunity Additional regulatory proteins Engineering technology In vivo protein engineering In vitro protein engineering Modes of action Pore formation Lipid II targeting lantibiotics activities Spore outgrowth inhibition Other bioactivities Conclusion References 4 Development of recombinant lantibiotics and their potent uses Introduction The genetics of lantibiotic biosynthesis Bioengineered lanthipeptides Heterologous production of lantibiotics by Lactococcus lactis Heterologous production of lantibiotics by Escherichia coli Heterologous production of lantibiotics by Streptomyces spp Heterologous production of lantibiotics by yeasts The activity of lantibiotics against pathogens Other therapeutic applications of lantibiotics Immune modulation Neuropathic pain relief Anticancer treatment Antiviral capacity Food preservation Conclusion References 5 Mechanism of action of the lantibiotics on the multidrug-resistant organisms Mechanism of development of drug resistance Introduction Antibiotic modification Antibiotic efflux Target modification Intrinsic and acquired resistance Molecular basis of drug resistance Resistance developed by chromosomal mutation Fluoroquinolones Rifamycins Horizontal gene transfer Recombination Biosynthesis of lantibiotics Use of lantibiotics in preventing biofilm Biofilm formation Application of antibiofilm agents to prevent biofilm formation Antibiofilm action of antimicrobial peptides against multidrug-resistant bacteria that produce biofilm Action of antimicrobial peptides on development of biofilm on the surface of medical implants Action of antimicrobial peptides against development of oral plaque Use of enzymes to prevent biofilm formation Antibacterial activity of lantibiotics and bacteriocins against human pathogens Types of lantibiotics and other bacteriocins produced from GPB and GNB Bacteriocins Different types of bacteriocins Bacteriocins synthesized by GPB Bacteriocins produced by GNB Method of action of lantibiotics Type-A(I) lantibiotics Membrane interaction and formation of pore Lipid II–mediated antimicrobial activity Type-A(II) lantibiotics Membrane interplay and formation of pore Lipid II interaction and inhibition in the biogenesis of cell wall Type-B lantibiotics Lipid II binding and inhibition of peptidoglycan formation Two-component lantibiotics Interaction with lipid II and generation of pore Suppression of spore germination Other biological roles Bioengineering of lantibiotics and future prospects Bioengineering: developing more effective lantibiotics Future use References 6 Lantibiotics, its role in the meat and poultry industry Introduction Lantibiotics Commonly occurring problems in the poultry and meat industry Sources of contamination The major bacterial contaminants related to poultry meat Bacterial contaminants Spoilage-causing bacteria Pathogenic bacteria Bacteriocins commonly used in the meat and poultry industry Reasons for using lantibiotics in the meat and poultry industry Role of lantibiotics in the poultry industry Role of lantibiotics in swine Conclusion References 7 Application of lantibiotics in canned food preservation Introduction Classification Type-A lantibiotics Type-B lantibiotics Some traditional lantibiotics used in food preservation Nisin Lacticin 3147 Lacticin 481 Lactococcin B Enterocins Subtilin Pediocin PA-1 Mode of action Type-A(I) Type-A(II) Biosynthetic pathway Modulation of lantibiotic biosynthesis Prepeptides and the leader sequence Enzymes used in the posttranslational synthesis of proteins Different lantibiotics in canned food preservation Usage of nisin in canned food Usage of nisin in canned vegetables Usage of nisin in dairy products Canned evaporated milk Hard cheeses Pasteurized cheese products Yogurt Heat-sterilized and flavored milk Usage of nisin in alcoholic beverages Beer Wine Other lantibiotics in canned meat preservation Preservation of raw canned meat Other lantibiotics used in canned seafood preservation Other lantibiotics used in canned dairy product preservation Hurdle technology to enhance food safety Fundamental applications in canned food Hurdle technology in canned food preservation Surface coating of vegetables Incorporation of carrageenan chitosan multilayer Use of hurdle technology combining with lantibiotics in food preservation Usage in food sterilization Usage of hurdle technology to ensure the quality and durability of canned milk products Concept of hurdle technology in the safety of meat Hurdle technology in mild acidification (pH 4.6) with minimal heat treatment Uses of some lantibiotics as hurdles Conclusion References 8 Lantibiotics and its role in dairy product preservation Introduction Advantages of using lantibiotics over chemical preservation What are lantibiotics? Classification of lantibiotics used for the preservation of dairy products Lantibiotics producing organisms used in the dairy industry Application of lantibiotics in the food industry Structure and functional roles of lantibiotics in dairy product preservation Nisin Bioengineering of nisin to overcome its limitations Enterocins Lacticin Pediocins Repurposing of lantibiotics as an alternate to the antibiotics Suitable host system Noncanonical amino acids—extended genetic alphabets Immobilized metal affinity chromatography immobilization Conclusion References 9 In vitro studies on a natural lantibiotic: paenibacillin Introduction Peptide antibiotics Lantibiotics: structure, function, and mode of actions Paenibacillin: a next-generation antimicrobial peptide with diverse potentials Biosynthesis of paenibacillin by Paenibacillus spp. Antimicrobial efficacy of paenibacillin Biotechnological approaches for enhancing the production of paenibacillin Conclusion and future perspectives References 10 Lantibiotics in antifungal therapy: a futuristic approach Introduction Lantibiotics: classification and structure Lantibiotics: synthesis Lantibiotics: potential target and action mechanism Traditional antifungal therapeutic agents: limitations Lantibiotics as antifungal therapeutic agent Pinensin Nisin Z Combination therapy Lantibiotics Traditional drugs Steroids Conclusion Authors contributions References 11 In silico studies of interaction of lantibiotics with virulent proteins Introduction Types of lantibiotics Bioactivity of lantibiotics Databases of lantibiotics Molecular docking and molecular dynamics Protein–peptide docking Types of protein–peptide docking methodology Local docking method Global docking method Template-based docking Protein–peptide docking software programs Molecular docking Challenges Limitation of docking Virulent proteins Interactions of lantibiotics with virulent proteins Conclusion References 12 Insights at the atomistic resolution of lantibiotics using multiscale simulations Introduction Lantibiotics against biofilm Structural and functional prospect of lantibiotic nisin Multiscale simulations of nisin Target molecule and initial guess Molecular dynamics simulations Nisin, epidermin, and gallidermin reveal similar building motif The source of epidermin and gallidermin advantage over nisin Conclusion References 13 Immunogenicity studies on lantibiotics Bacteriocins – an introduction Class I lantibiotics Structural aspects Unusual amino acids Organization of lantibiotic gene clusters The biosynthetic pathway Prepeptides and role of leader the sequence Type-A(I) leaders Type-A(II) leaders Posttranslational modification pathways enzymes LanB and LanC enzyme products LanM enzyme Modification of two-component lantibiotics EpiD-curated oxidative decarboxylation Activation and translocation Proteolytic cleavage by specific leader proteases LanT: the ABC transporter Activation and export of cytolysin Regulation of lantibiotic biosynthetic pathways Action mechanism of bacteriocins Pore-forming lantibiotics Nisin-pore formation pathway Other pore-forming lantibiotics Type-B lantibiotics The cinnamycin subtype The mersacidin subtype Two-component bacteriocins Lactococcin G Future prospects References Further reading 14 Case studies: application of lantibiotics as novel drugs Discovery of lantibiotics Biosynthesis of gene clusters and ring structures Gene organization Antibiotic resistance Causes of antibiotic resistance Antibiotic resistance leading to the bacterial infections Lantibiotics in therapeutics Role of lantibiotics against Gram-positive bacteria Role of lantibiotic against Gram-negative bacteria Role of lantibiotic in therapeutic applications Conclusion Conflict of interest References 15 Recent updates in understanding of molecular genetics of lantibiotics production Introduction Classifying lantibiotics Lantibiotic and nonlantibiotic monopeptides Lantibiotic and nonlantibiotic dipeptides Regulation, manufacture, and biosynthesis Mutacin immunity Conclusion References 16 Methods for identification of the modes of action of lantibiotics Introduction Mode of action of lantibiotics Methods for identification of mode of action of lantibiotics in Gram-positive bacteria Analysis of lanthipeptide-lipid-II interaction In vitro biosynthesis assay Isothermal titration calorimetric assay Lipid-II cycle interfering antibiotic response regulator and sensor (LiaRS) reporter assay Molecular detection of lipid-II interaction with lanthipeptide Enzyme-linked immunosorbent assay Thin-layer chromatography Spot-on-lawn assay Microscopic analysis Binding assay with plasma membrane lipid components Analysis of pore formation Potassium release experiment Pore formation assay using fluorescence dyes Methods for identification of mode of action of lantibiotics in Gram-negative bacteria Lipopolysaccharide binding assay Fluorescent dye-loaded liposome assay Conclusion References 17 Computational modeling for exploring the therapeutic repertoire of lantibiotics Introduction Brief overview of the different classes of lantibiotics Type A lantibiotic Type B lantibiotic Mode of action of lantibiotics Membrane interaction of lantibiotics occurs via the following steps Lantibiotics as therapeutic molecules Process of computational modeling Computational screening Comparative homology modeling Model refinement and selection Structure validation Case studies Molecular modeling, simulation and druggable pocket prediction of nisin A, nisin B and plantaricin C Molecular modeling, simulation and druggable pocket prediction of mersacidin and epidermin Studies on interactions of cinnamycin and ACE2 Therapeutic landscape revealed through structural analysis Conclusion References Further reading 18 Combinations of nanobiomolecules as next-generation antimicrobial agents Introduction Antimicrobial nanobiomolecules Gold nanoparticles Silver nanoparticles Copper nanoparticles Zinc oxide nanoparticles Iron oxide Others Conclusion References 19 Lantibiotics: the way forward for clinical trials and clinical approval process Introduction Short write-up on lantibiotics Therapeutic effects of lantibiotics Future prospects of lantibiotics Preclinical trials Where do we stand (an overview of current preclinical studies) The layout of in vitro preclinical trial Types of preclinical study Ethics committee Monitoring animal use Good laboratory practice Data analysis and report preparation The current landscape of clinical trials Decentralized trials Advantages Barriers Designing clinical trials Uncontrolled trials Controlled trials Randomized clinical trials Designs and types of randomized clinical trials Trial objectives and purpose Patient recruitment and withdrawal Clinical research phase studies Phase I Phase II Phase III Phase IV Assessment of safety Statistics and safety of clinical trial process Clinical trial review team Institutional review board/ethics committee Data and safety monitoring board Regulatory authorities Quality control and quality assurance Ethics Multiple challenges to the clinical trials Patient recruitment Compliance with several rules and regulations Lack of community physician involvement Funding Pharmacovigilance study Final drug approval Future hope Conclusion References Further reading 20 Properties, classification and applications of lantibiotics from Gram-positive bacteria Introduction Lantibiotic structure and function Type A Type B Classification of lantibiotics Class I Class II Class III Class IV Lantibiotic biosynthesis Mode of action Applications Food industry Antimicrobial potential Immunomodulatory potential Neuropathic pain reliever Contraceptives Alternative cancer therapy Skincare/cosmetic industry Conclusions and future perspectives References 21 Lantibiotics production—optimization and scale-up research: cutting edge and challenges Introduction The structure and functional properties that influence lantibiotics production Class I bacteriocins Class II bacteriocins Class III bacteriocins Class IV bacteriocins Properties that influence production The chemical synthesis and the economic feasibility of using bacteriocins In vitro bioengineering synthesis Combined bioprocess strategies to increase the amount of yield of Lantibiotics The viability of the bio-production process of lantibiotics Current applications of bioengineered Lantibiotics Treatment of human diseases Preservation of food Plant growth promotion Summary and conclusion References 22 Production and optimization of lantibiotics Introduction Optimization of production of potential lantibiotics US Food and Drug Administration approved lantibiotics Bacteriocin Nisin Pediocin Mutacin Other lantibiotics use in food industry Conclusion and future perspectives References 23 Analytical techniques in identifying and purifying the proteins Sodium dodecyl sulfate–polyacrylamide gel electrophoresis Western blot 2D-gel electrophoresis Enzyme-linked immunosorbent assay Mass spectroscopy FTIR spectroscopy Nuclear magnetic resonance Circular dichroism UV and visible spectroscopy Fluorescence spectroscopy Protein estimation methods Bradford assay Lowry method Bicinchoninic acid assay Peptide sequencing by Edman degradation Purification of proteins and peptides through chromatography Chromatographic techniques in protein purifications Reference Index Back Cover