Antibiotics

这是一篇关于Antibiotics的思维导图，主要内容有Antimicrobial susceptibility patterns、spectrum of action、QUNATIFY antibiotics' effects等。

Antibiotics

• Antimicrobial susceptibility patterns
  • Bacteriostatic
    • Only inhibits growth but not kill bacteria
      • like to only binds the ribosome and inhibits protein synthesis
  • Bacteriocidal
    • kill bacteria but not lysis cell
      • because it binds to the cellular targets too tight
  • Bacteriolytic
    • kill and lysis the cell
• spectrum of action
  • Broad spectrum
    • Can against both gram+ and gram-
  • Narrow spectrum
• QUNATIFY antibiotics' effects
  • methods
    • tube dilusion
      • turbidity of tubes
    • Disk-diffusion/ agar diffusion
      • zones of growth inhibition of inhibitor organism
        • susceptible
        • intermediate
        • resistent
  • Minimum Inhibitory Concentration (MIC)
    • observed growth reduction
  • Minimum Bactericidal Concentration (MBC)
    • Kills all, no recovery
• Achieve selective toxicity
  • Target bacterial
    • Cell wall synthesis
      • β-Lactams inhibits transpeptidase which cross-links gram(+) peptidleglycan.
        • penicillin contains a β-lactams ring
      • most astonishing bacterial defense
        • producing enzyme β-lactamase
          • so use the enzymes inhibitor: e.x. potassium clavulanate to combine penicilin
    • Plasma membrane
      • effects selective permeability
      • leakage of important solutes essential for cells survival
    • ribosome
      • 50s
      • 30s
        • Streptomycin Causes Misreading of mRNA
      • translation initiation
      • translation elongation
        • Tetracyclin..
          • blocks incomming tRNA binds to A site
        • Erythromycin
          • blocks ribosome translocation
          • Resistance due to enzymatic methylation of 23S rRNA
    • DNA replication
      • gyrase
        • Ciprofloxacin
          • resistance due to mutations in the gyrase A subunit.
          • extremely broad ranged
        • Novobiocin
          • compete with ATP for binding to the B subunit of this enzyme and inhibit the ATP-dependent DNA supercoiling catalysed by gyrase.
          • resistance due to mutations in B subunit
    • RNA transcription
      • RNA pol
        • Rifampin
          • interferes with transcription initiation complex
          • fast resistence for mutations in RNA polymerase
            • so it self should not be used
    • metabolites
      • Tetrahydrofolate (THF) synthesis inhibitor
        • Sulfonamides
          • strucural analogous of paba
        • Trimethoprim
          • inhibits bacterial dihydrofolic acid reductase (DHFR; 105 greater effect on prokaryotic than eukaryotic enzyme)
• The function of antibiotics for the microbe
  • Repressed during active growth, activated during nutrient limitation
    • espectially N and P limitations
    • Against competitors
    • some exeptions
• Chemistry
  • Peptides
  • Amino acid derivative
  • Proteins
  • Polykitide derivative
  • Carbohydrate derivative
  • Aromatic derivative
• Applications
  • drops infectious desease motality from 0.797% to 0.036%
  • Antibiotic combinations
    • Reduce emergence of antibiotic resistance
    • results
      • Synergism
        • target different steps of route
      • Antagonism
        • ex bactericidal+bacteriostatic
  • Super bugs: microbes with multiple resistences
    • MRSA
      • Methicillin Resistant Staphylococcus aureus
      • Prevalence
        • Community acquired (CA) MRSA
          • Pandemic: 21-29% in adults and 35-50% in children
          • not multi-drug resistence
        • Healthcare associated (HA) MRSA
          • multi-frug resistence
      • Genetic elements
        • mec gene – staphylococcal chromosomal cassette (SCCmec)
          • 5 types
          • MecA encodes PBP2a
            • alternative PBP(enzyme penicilin targets)
            • Resulting peptidoglycan is structurally different but functional.
            • B-lactamase genes can down regulates MecA gene transcripts
      • new antibiotics
        • •Linezolid •Quinupristin-dalfopristin •Daptomycin •Lysostaphin
    • VISA
      • Vancomycin intermediate susceptible strains
        • a little resistence to vancomycin
      • altered peptidoglycan biosynthesis which causes thicker cell walls and decreased drug exposure to the cytoplasmic membrane
    • VRSA
      • Vancomycin resistence strain
        • MIC>=32 ug/ml
      • Vancomycin binds terminal dipeptide in peptide side-chain and inhibits transglycosylation and transpeptidation
        • Vancomycin is unable to bind to its target site due to an altered terminal peptide.
    • Superbug-TB
      • Pathogen grows in macrophage and may become persistent
      • Thick lipid-rich outer membrane with mycolic acid limits uptake of antibiotics
      • Narrow porin channel transports b-lactams
  • against superbugs
    • Virulence genes target Antisense RNA
    • Develop New antibiotics
    • Use cocktails
    • Ristrict antibiotics use
    • track resistence data