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• Antimicrobials


  Natural and synthetic products used to kill or inhibit the growth of microorganisms
• Learning Objectives


  • To explore how natural and synthetic products are used as antimicrobials
  • To develop knowledge of different antimicrobials: natural and synthetic
  • Describe different types of antimicrobials and their uses
  • Make sound judgments about the possible uses of antimicrobials in terms of potential development of antimicrobial resistance
  • Demonstrate knowledge of how humans interact with microbial communities
• Outline


  • Antimicrobials
  • Plant derived products
  • Metal ions
  • Natural products
  • Animal based
  • Bacteriocins
• We won't cover in detail: Biocides, Disinfectants, products that are used on inanimate objects or surfaces, Antiseptics, products that destroy or inhibit the growth of microorganisms in or on living tissue, Sterilisation, physical or chemical process that completely destroys or removes all microbial life, including spores
• McDonnell G, Russell AD. Antiseptics and Disinfectants: Activity, Action, and Resistance. Clinical Microbiology Reviews. 1999;12(1):147-179.
• Definitions


  • Antibiotic
  • Antimicrobial
  • Bactericidal
  • Bacteriocin
  • Bacteriolysin
  • Bacteriophage
  • Bacteriostatic
  • Biocide
  • Biofilm
  • Essential Oil
  • L-amino acid oxidase
  • Natural
  • Nanotechnology
  • Resistance
  • Sensitive
  • Tolerant
• Antibiotic


  A low molecular substance often produced by a microorganism that at a low concentration inhibits or kills other bacteria
• Antimicrobial


  Any substance of natural, semisynthetic or synthetic origin that kills or inhibits the growth of microorganisms but causes little or no damage to the host – more general encompassing parasites etc.
• All antibiotics are antimicrobials, but not all antimicrobials are antibiotics
• Antibiotic resistance


  Occurs when bacteria change in response to the use of these medicines
• Antimicrobial resistance (AMR)


  A broader term, encompassing resistance to drugs to treat infections caused by other microbes as well as parasites (e.g. malaria), viruses (e.g. HIV) and fungi (e.g. Candida)
• Antimicrobials


  • Plant-based
  • Metal-based
  • Nanotechnology-based
  • Animal-based
  • Microbe-based (non-antibiotic)
• Plant-based antimicrobials - History


  e.g. isoquinoline alkaloid emetine obtained from the Cephaelis ipecacuanha has been used for many years to treat dysentery and the treatment of abscesses due to the spread of parasitic Entamoeba histolytica infections
• Plant-based antimicrobials - Modern day uses


  Include the use of plant derived alkaloids, aldehydes, alcohols, terpenes, steroids, tannins, and phenolic compounds
• Essential oils (EOs)


  Contain many constituents, many of which individually are antimicrobial, but in combination work synergistically
• Essential oil constituents


  • Menthol: an alcohol from mint
  • Citral: an aldehyde from citrus fruits
• Curcumin


  A yellow compound derived from turmeric, a natural phenolic compound with potent anti-tumour, anti-inflammatory, anti-oxidant, anti-microbial (bacteria, yeast, virus) properties
• Curcumin with Silver ions

  Synergistic effects
• Curcumin with antibiotics


  Synergistic effects
• Metal ions


  Examples include: copper, silver, gold, platinum, palladium, zinc
• Metal ions


  Synergistic effects with other technologies (e.g. silver)
• Metal ion combinations


  • Silver ions, Ag+
  • Silver nanoparticles
  • Silver nanoparticle-Chitosan composite particles
  • Silver ions with various other metal ions (but not all)
  • Silver and antibiotics
• Mijnendonckx et al. (2013) Antimicrobial silver: uses, toxicity and potential for resistance. Biometals. 26: 609-621
• AgNO3 and Chitosan composite spheres

  Synergism?
• Wang et al. (2015) Synthesis and anti-fungal effect of silver nanoparticles–chitosan composite particles. Int J Nanomed 10: 2685-2696
• Not all that glitters is 'a metal ion'...
• Natural compounds


  • Animal-based
  • Microbe-based (non-antibiotic)
• Escapin


  An L-Amino Acid Oxidase (LAAO) from the sea hare, flavin cofactor dependant, oxidises L-arginine and L-lysine to produce H2O2, bacteriostatic in minimal media, bactericidal in rich media containing L-arginine and L-lysine, effective against Gram-positive and Gram-negative bacteria, Vibrio harveyii, Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa, also inhibited the growth of yeast and fungi
• Mode of action of LAAOs


  1. Convert L-amino acids (l-alanine in this example) to pyruvic acid and hydrogen peroxide (H2O2)

  2. The intracellular concentration of H2O2 is tightly controlled by various enzymatic and nonenzymatic antioxidant systems and is assumed to vary between 1 and 700 nM

  3. Intracellular steady-state concentrations of H2O2 above 1 μM are considered to cause oxidative stress inducing growth arrest and cell death
• Snake venom LAAOs


  Snake venoms contain L-amino acid oxidases, whole venom as well as the L-amino acid oxidase from Bothrops marajoensis was able to inhibit the growth of several microorganisms, including S. aureus, Candida albicans, Pseudomonas aeruginosa and Leishmania sp.
• Costa-Torres et al. (2010) Antibacterial and antiparasitic effects of Bothrops marajoensis venom and its fractions: Phospholipase A2 and L-amino acid oxidase. Toxicon 55: 795–804
• Antibacterial activity of snake venom LAAO


  Minimal Inhibitory Concentration (MIC) between 50-100 ug/ml, similar to antibiotic Amikacin at 25-50 ug/ml
• Chitosan


  Derived from deacetylation of Chitin, antimicrobial activity based on the type of microorganism, the molecular weight, and the degree of deacetylation
• Bacteriocins


  Example: Nisin is a class of antimicrobial termed Lantibiotics which contain an unusual amino acid: Lanthionine (Lan)
• Bacteriocins


  • Nisin
  • Abp118 from Lactobacillus salivarius UCC118
  • Thuricin from Bacillus thuringiensis
• Cotter, P.D., Ross, P. and Hill, C. (2013) Bacteriocins — a viable alternative to antibiotics? Nat Rev Micro. 11: 95-105
• • Lactobacillus salivarius UCC118: Abp118
  • Thuricin, which is produced by Bacillus thuringiensis
• Bacteriocins and microbiome


  Narrow Spectrum: useful for protecting the gut microbiome?
• • For the exams...
  • Learn key definitions
  • Understand how natural and synthetic products are used as antimicrobials
  • Understand possible uses of antimicrobials, and in context of antimicrobial resistance