Biol 251 Chapter 20

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  1. How do antibiotic works?
    • Antimicrobial drugs are either bactericidal (they kill microbes directly) or bacteriostatic (they prevent microbes from growing)
    • Inhibiting cell wall synthesis
    • Inhibiting protein synthesis
    • Injuring the plasma membrane
    • Inhibiting nucleic acid synthesis
    • Inhibiting the synthesis of essential metabolites
  2. Inhibiting cell wall synthesis (Bactericidal)
    • Penicillin, the first true antibiotic to be discovered and used it one does not also consider the sulfa drugs, is an example of an inhibitor of an inhibitor of cell wall synthesis
    • Penicillin and certain other antibiotics prevent the synthesis of intact prptidoglycan; consequently the cell wall is greatly wakened and the cell undergoes lysis
    • Because penicillin targets the synthesis process, only actively growing cells are affected by these antibiotics
    • Because human cells do not have peptiogylcan cell walls, penicillin has very little toxicity for host cells
    • Targets NAG, NAM stage, final stage of peptidoglycan synthesis. Penicillin stop cross-linking of peptidoglycan
  3. Inhibiting protein synthesis (Bacteriostatic)
    • Antibiotics targeting the 70s ribosomes can therefore have adverse effects on the cells of the host
    • Among the antibiotics that interfere with protein synthesis are chloraphenicol, erythromycin, streptomycin, and the tetracyclines
  4. Injuring the plasma membrane
    Certain antibiotics, especially polypeptide antibiotics, bring about changes in the permeability of the plasma membrane that results in the loss of important metabolites form the microbial cell
  5. Inhibiting nucleic acid synthesis (Bacteriostatic)
    • A member of antibiotics interferes with the processes of DNA replication and transcription in microorganisms
    • Some drugs with this mode of action have an extremely limited usefulness because they interfere with mannalian DNA and RNA as well
  6. Inhibiting the synthesis of essential metabolites
    • An example of competitive inhibitions the relationship between the antimetabolite sulfaniamide (a sulfa drug) and para-aminobenzoic acid (PABA)
    • PABA is the substrate for an enzymatic reaction leading to the synthesis of folic aci, a vitamin that functions ans a co-enzyme for the synthesis of the purine and pyrimidine bases of nucleic acids and many amino acids
  7. How does penicillin works?
    • Penicillin containing β-lactam ring; types are differentiated by the chemical side chains attache to the ring
    • Prevent the cross-linking of peptidoglycans, interfering with cell wall construction (especially gram positive)
  8. Natural penicillin
    • Extracted from penicillum cultures - penicillin G (injected), penicillin V (oral)
    • Narrow spectrum of activity
    • Susceptible to penicillinase (β-lactamase)
    • Natural penicillin have some disadvantages. Chief among them are their narrow spectrum of activity and their susceptibility to penicillinase 
    • Penicillinases are enzymes produced by many bacteria, most notably staphylococcus species, that cleave the β-lactamin ring of the penicillin molecule
    • Because of this characteristic, penicillinases are sometimes called β-lactamase
  9. Semi-synthetic penicillin
    • Contains chemically added side chains, making them resistance to penicillinase
    • Semi-synthetic penicillin can interrupt synthesis of the molecule by penicillum and obtain only the common penicillin nucleus for use
    • They can remove the side chains form the completed natural molecules and then chemically ad other side chains that make them more resistant to  penicillinase or the scientists can give them an extended spectrum
    • Thus, the term semi-synthetic; part of the penicillin is produced by the mold, and part is added synthetically
  10. Effects of penicillinase on penicillin
    Bacterial production of this enzyme, which is breaking the β-lactamin ring is by far the most common form of resistance to penicillin
  11. Penicillinase-Resistant penicillin
    • methicillin and oxacillin
    • Resistant of staphylococcal infections to penicillin soon become a problem because of a plasmid-borne gene for β-lactamase.
    • Antibiotics that were relatively resistant to this enzyme, such as the semi-synthetic penicillin, methicillin, were introduced, but resistance to them also soon appeared; thus the organisms were termed methicillin-resistant staphylococcus aureus (MRSA)
  12. Extended-spectrum penicillin
    • Effective against gram-negative as well as gram-positive; aminopenicillin - ampicillin, amoxillin
    • To overcome the problem of the narrow spectrum of activity of natural peniillin, broader spectrum semi-synthetic penicillin have been developed
    • These new penicillin are effective against many gran-negative bacteria as well as gram-positive ones, although they are resistant to penicillinases
    • These broader spectrum penicillin are modification of the structure of ampicillin
  13. Penicillin plus β-lactamase inhibitors
    • Contain clavulanic acid, a non competitive inhibitor of penicillinase
    • Potassium clavulanateis non competitive inhibitor of penicillinase with essentially no antimicrobial activity of it's own.
  14. What are the mechanisms of antibiotic resistant?
    • Enzymatic destruction or inactivation of the drug
    • Prevention of penetration to the target site within the microbe
    • Alteration of the drug's target site
    • Rapid Efflux (ejection) of the antibiotic
    • Variations of mechanisms of resistance
  15. Enzymatic destruction or inactivation of the drug
    • Mainly effect natural products susch as penicillin and cephalosporine
    • β-lactam ring is the target for β-lactamase enzymes that selectively hydrolyze it when β-lactamin ring balance off it became active
    • β-lactamase is antibiotic degrading enzyme
  16. Prevention of penetration to the target site within the microbe
    Gram-negative bacteria are relatively more resistant tot antibiotic because of the nature of their cell wall, which restrict absorption of many molecules to movements through openings called proins
  17. Alteration of the drug's target site
    • Modifying penicillin binding protein (PBP) on the cell membrane, β-lactamin antibiotics act by binding with the PBP, which is required to initiate the cross-linking of peptidoglycan and form the cell wall
    • MRSA strains become resistant because they have an additional modified PBP (methicillin)
    • Penicillin targets PBP which can find peptidoglycan cell wall in bacteria because protein alternate penicillin binding protein, it does not recognize
  18. Rapid Efflux (Ejection) of the antibiotic
    • Certain proteins in the plasma membranes of gram-negative bacteria as pumps that expel antibiotics, preventing them from reaching an effective concentration
    • This mechanism was originally observed with tetracycline antibiotics, but it confers resistance among practically all major classes of antibiotics
    • Bacteria normally have many such efflux pumps to eliminate toxic substance
  19. Variations of mechanisms of resistance
    Resistant mutants will increasingly replace the susceptible normal population; Developing antibiotic resistant mutant during antibiotic therapy
  20. There are only a few mechanisms of microbial resistance to antimicrobial agents
    • Blocking the drug's entry into the cell
    • Inactivation of the drug by enzymes
    • Alteration of the drug's target site
    • Efflux of the drug from the cell
    • Alteration of the metabolic pathways of the host
    • The mechanisms of bacterial resistance to antibiotics are limited. Knowledge of these mechanisms is critical for understanding the limitations of antibiotic use

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Biol 251 Chapter 20
2016-05-08 22:56:56
Antimicrobial drug

Biol 251 Chapter 20
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