Week 9

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Created by
SJ

Cards (16)

  • Significance of antibiotic resistance
    • Antibiotic resistance is predicted to kill 10 million people worldwide every year by 2050 without action
    • It causes more deaths than cancer and diabetes
    • Since 2014 (UK), Human antibiotic use decreased by 7% and Antibiotics used in farming decreased by 40%.
  • Antibiotics are Secondary Metabolites
  • Penicillins were discovered by Alexander Flemming in 1928 when he noticed that bacteria did not grow on his petri dish containing staphylococcus aureus because it was contaminated with Penicillium fungi which produced penicillin
  • The discovery of penicillin led to the development of other antibiotics including tetracyclines, amino glycosides, macrolides, sulphonamides and quinolones
  • An antibiotic's mode of action works by impacting bacterial:
    1. DNA synthesis
    2. RNA synthesis
    3. Protein synthesis
    4. Membrane
    5. Cell wall
  • Novel Sources of Antibiotics
    • Lipid/sugar binding
    • Novel modes of action – None clinical
    • Biofilm disruption
    • Protein-protein interaction (PPI) inhibitors
    • Phage therapy
    • CRISPR-Cas9
    • Halobacteriovorax – Predatorial bacteria
  • Major Problems with AMR (specifically to antibiotics)
    • There is reported resistance for all clinically prescribed antibiotics. Incidence is rising by approximately 1-5% for each disease.
    • Dual resistance to combinatorial therapies of β-lactam and β-lactam inhibitors (sulfabactam) is common.
    • Poor economic viability for novel antibiotic discovery.
    • Lack of awareness and understanding in society.
    • Antibiotics increase food production by reducing the loss of energy from gut bacteria and preventing disease. Food production is vital to support the current world population.
  • Factors leading to AMR (specifically to antibiotics)
    • Exposure to sub-optimal levels of antimicrobial and microbes carrying resistance genes
    • Prescription not taken correctly
    • Antibiotics for viral infections and/or sold without medical supervision
    • Spread of resistant microbes in hospitals from poor hygiene
    • Lack of quality control in manufacture/outdated antimicrobials
  • Other factors leading to AMR (specifically to antibiotics)

    • poor surveillance/defective susceptibility assays
    • Poverty/war
    • antibiotics in food
    • Antibiotics in animal feeds and sprayed on plants to prevent infection and promote growth
    • Multi drug-resistant Salmonella typhi found in 4 states in 18 people who ate beef fed antibiotics
  • WHO priority bacterial pathogens are divided into:
    • Priority 1: critical
    • Priority 2: High
    • Priority 3: Medium
  • Priority 1: CRITICAL
    • Acinetobacter baumannii, carbapenem-resistant
    • Pseudomonas aeruginosa, carbapenem-resistant
    • Enterobacteriaceae, carbapenem-resistant, ESBL-producing
  • Priority 2: HIGH
    • Enterococcus faecium, vancomycin-resistant
    • Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant
    • Helicobacter pylori, clarithromycin-resistant
    • Campylobacter spp., fluoroquinolone-resistant
    • Salmonellae, fluoroquinolone-resistant
    • Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant
  • Priority 3: MEDIUM
    • Streptococcus pneumoniae, penicillin-non-susceptible
    • Haemophilus influenzae, ampicillin-resistant
    • Shigella spp., fluoroquinolone-resistant
  • The Resistome Concept

    The resistome has been suggested to include protoresistance, gene(s) that have the potential for resistance via evolution, as well as clinical, environmental, and intrinsic resistance genes
  • Types of resistance
    • Acquired resistance: vertically or horizontally transferred, taxa-nonspecific
    • Intrinsic resistance: only vertically transmitted, taxa-specific
    • Silent/cryptic resistance: phenotypically sensitive, functional but not expressed
    • Protoresistance: phenotypically sensitive, little/no activity until mutated
  • Regarding the occurrence of Antimicrobial Resistance Genes, critical findings suggest:
    • AMR is ancient and ubiquitous in various microbiomes
    • Antibiotic resistome is complex and diverse
    • Environmental resistome is the origin and a reservoir of ARGs
    • Resistome is generally determined by the microbial community structure in the natural environment
    • Anthropogenic activities shape the environmental resistome
    • Mobile genetic elements are responsible for ARG transmission
    • ARGs flow among humans, animals, and the environment