Pharmacognosy

• Antibiotics that inhibit cell wall synthesis

  Antimicrobial drugs that selectively interfere with synthesis of the bacterial cell wall, a structure that mammalian cells do not possess

  
• Cell wall


  • Composed of a polymer called peptidoglycan that consists of glycan units joined to each other by peptide cross-links
• Types of antibiotics that inhibit cell wall synthesis

  • β-lactam antibiotics
  • Non β-lactam antibiotics

  
• β-lactam antibiotics


  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Monobactams

  
• Non β-lactam antibiotics


  • Vancomycin
  • Teicoplanin
  • Bacitracin
  • Polymyxin and Colistin

  
• Antibiotics that inhibit cell wall synthesis

  Antimicrobial drugs that selectively interfere with synthesis of the bacterial cell wall, a structure that mammalian cells do not possess

  
• β-lactam antibiotics


  Have a β-lactam ring in their chemical structure

  
• Cell wall


  • Composed of a polymer called peptidoglycan that consists of glycan units joined to each other by peptide cross-links
• Penicillin


  The first antibiotic developed and used clinically, discovered accidentally by Alexander Fleming
• Types of antibiotics that inhibit cell wall synthesis

  • β-lactam antibiotics
  • Non β-lactam antibiotics

  
• Penicillins


  • Effective, cheap, and tolerable (have little side effects)
  • Use decreased due to emergence of bacterial resistance
• β-lactam antibiotics


  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Monobactams

  
• Classification of penicillins


  • Natural penicillins
  • Aminopenicillins
  • β-lactamase resistant penicillins
  • Antipseudomonal penicillins
• Non β-lactam antibiotics


  • Vancomycin
  • Teicoplanin
  • Bacitracin
  • Polymyxin and Colistin

  
• Mechanism of action of penicillins

  Interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross-linkage), resulting in exposure of the osmotically less stable membrane. Cell lysis can then occur, either through osmotic pressure or through the activation of autolysins.

  
• β-lactam antibiotics


  Have a β-lactam ring in their chemical structure

  
• Penicillin-binding proteins (PBPs)


  • Bacterial enzymes (transpeptidase) involved in the synthesis of the cell wall and in the maintenance of the morphologic features of the bacterium
  • Alterations in some of these PBPs provide the organism with resistance to the penicillins

  
• Production of autolysins


  • Degradative enzymes that participate in the normal remodeling of the bacterial cell wall
  • In the presence of a penicillin, the degradative action of the autolysins proceeds in the absence of cell wall synthesis, resulting in cell lysis

  
• Penicillin


  The first antibiotic developed and used clinically, discovered accidentally by Alexander Fleming
• Antibacterial spectrum of penicillins

  • Determined by their ability to cross the bacterial peptidoglycan cell wall to reach the PBPs in the periplasmic space
  • Factors that determine susceptibility include size, charge, and hydrophobicity of the particular β-lactam antibiotic

  
• Penicillins


  • Effective, cheap, and tolerable (have little side effects)
  • Use decreased due to emergence of bacterial resistance
• Classification of penicillins


  • Natural penicillins
  • Aminopenicillins
  • β-lactamase resistant penicillins
  • Antipseudomonal penicillins
• Mechanism of action of penicillins

  Interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross-linkage), resulting in exposure of the osmotically less stable membrane. Cell lysis can then occur, either through osmotic pressure or through the activation of autolysins.

  
• Penicillin-binding proteins (PBPs)


  • Bacterial enzymes (transpeptidase) involved in the synthesis of the cell wall and in the maintenance of the morphologic features of the bacterium
  • Alterations in some of these PBPs provide the organism with resistance to the penicillins

  
• Production of autolysins


  • Degradative enzymes that participate in the normal remodeling of the bacterial cell wall
  • In the presence of a penicillin, the degradative action of the autolysins proceeds in the absence of cell wall synthesis, resulting in cell lysis

  
• Antibacterial spectrum of penicillins

  • Determined by their ability to cross the bacterial peptidoglycan cell wall to reach the PBPs in the periplasmic space
  • Factors that determine susceptibility include size, charge, and hydrophobicity of the particular β-lactam antibiotic

  
• Susceptibility of microorganisms to penicillins

  • Gram-positive microorganisms are susceptible
  • Gram-negative microorganisms have an outer lipopolysaccharide membrane that presents a barrier, but have proteins (porins) that allow transmembrane entry