Lantibiotics as Alternative Therapeutics

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
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