antibacterial modes of infection

• antimicrobial 


  Any chemicals which kill or inhibit microbial growth in or on a body surface
• antibacterial


  any chemical which specifically targets bacteria and kills or inhibits its growth
• antibiotic


  a drug used to treat bacterial infections
• what type of bacteria do most antibiotics kill


  mostly active it is hard to treat dormant infections
• bactericidal 


  kill bateria
• bacteriostatic


  slow down or stall bacteria growth
• selective toxicity 


  selectively kills or inhibits the target organism, whilst causing no or minimal harm to the host
• why is it harder to find selective toxicity in anti fungals and antivirals

  antifungals - are eukorcytes so a lot of simmilarity between us and fungus so hard to find a specific part to target

  antivirals - virus hasnt got much to it to find something that targets it
• ideal properties of antibacterials


  specific - can interact with a defined target

  
  

  selective - selectively kills or inhibits the target organism, whilst causing no or minimal harm to the host

  
  

  bactericidal - kills bacteria

  
  

  minimal emergence of resistance to drug
• ideal activities of antibacterials


  non-toxic to host

  long plasma half-life

  good tissue distribution

  low plasma protein binding

  oral and parenteral

  no interference with other drugs
• site of action on bacteria cells

  many drugs:

  
  

  cell wall

  nucleic acid

  protein syntheysis

  
  

  few drugs:

  
  

  cell membrane
• why do we have few drugs which target the bacteria cell membrane 


  bacteria cell membrane is very similar to human cell membrane so hard to target
• inhibitors of cell wall synthesis


  B- lactams - penicillins

  
  

  glycopeptides - vancomycin, teicoplanin

  
  

  fosfomycin

  
  

  cycloserine

  
  

  bacitracin
• gram -ve bacteria

  pink = , has pores which allows drug to come out easily, lipopolysacharides (LPS) adds another outer membrance and is more hydrophobic and shields from lysosomes

  
• gram +ve bacteria


  purple - , gram-positive bacteria lack a hard protective outer layer. The peptidoglycan layer that surrounds gram-positive bacteria is capable of absorbing antibiotics and cleaning products, which are fatal to them, bigger pepiloglycan layer, Teichoic acids = signalling

  
• how does peptiloglycan bacteria cell wall look like?


  alternating amino sugars with glycosidic bond connecting them, peptide chains cross-link with each other to join more aa
• what enzyme crosslinks the amino acid side chains


  transpeptidases
• what enzyme joins the amino acid monomers onto the peptidoglcan 


  glycosylases
• inhibitors of cell wall synthesis


  B lactams - penicillins, monobactams

  
  

  glycopeptides - vancomycin

  
  

  fosfomycin

  
  

  cycloserine

  
  

  bacitracin
• what do B lactams do to the cell wall in bacteria?

  inhibit synthesis of cell wall by inhibiting crosslink of peptide side chains

  
  

  1- bind to and inhibit the action of transpeptidases (cross link aa side chains) effects the formation of peptidoglycan

  
  

  2- gets incorporated into the peptide side chain which prevents the stable formation of peptidoglycan
• indirect mode of action of B lactate


  stimulates the bacteria to produce autolysins ( breaks down cell wall causing cell lysis)
• mode of action of glycoproteins in inhibiting cell wall synthesis


  prevents cross linking of peptide chains and prevents glycosylase from adding aa onto peptidoglycan chain
• examples of drugs acting on cell membrane

  polymyxins - treats serious gram -ve infections

  lipopetides
• how do polymyxins disrupt cell membrane


  polymyxin binds to lipid A, distorts cell m, penetrates cell wall which disrupts membrane integrity, allows leakage if cytoplasmic contents
• what do polymyxins treat?


  Serious gram -ve infections
• what do antibiotics acting on nucleic acids affect?


  nucleic acid synthesis, DNA replication, RNA polymerase, DNA
• Which enzymes and how do they effect DNA replication in bacteria cells?

  drugs bind to and inhibit DNA gyrase(removes DNA supercoils before replication fork is formed) and/or topoisomerase IV (separates DNA after replication)

  
  

  inhibits DNA replication causes cell lysis
• how do tetracylines(drugs) inhibit protein synthesis in bacteria cell?

  binds reversibly to trna to a site which inhibits protein synthesis

  selective binding

  effects = bacteriostatic - slow down or stalls bacteria growth
• how do aminoglycosides (drugs) inhibit protein synthesis in bacteria cells?


  bind irreversibly to trna a site, causes misreading of codons which increases bacterial membrane permeability