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ANTIMICROBIAL AGENTS AND CHEMOTHERAPY BY: DR ALPANA VERMA Head, Department of Microbiology  and Parasitology
[object Object],[object Object],[object Object],[object Object],CHEMOTHERAPEUTIC  AGENTS
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object]
[object Object],Later on for screening of about 10,000 strains of soil bacteria and fungi by Waksman Nobel Prize was given to him in 1952, and his success led to a worldwide search for Microorganisms producing chloramphenicol, neomycin, terramycin, and tetracycline etc.
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Characteristics of Antimicrobial Drugs or Agents
Characteristics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Characteristics: ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
What is the ideal antibiotic? ,[object Object],[object Object],[object Object],[object Object]
What is the ideal antibiotic? ,[object Object],[object Object],[object Object],[object Object],[object Object]
Principles / Definitions ,[object Object],[object Object]
Principles / Definitions ,[object Object],[object Object],[object Object],[object Object]
Principles / Definitions ,[object Object],[object Object],[object Object]
Combination Therapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
Measurement of antimicrobial activity Minimal inhibitory concentration: the lowest concentration of an antimicrobial compound that prevents growth of a microbe  in vitro 0.05 0.1 0.2 0.4 0.8 1.6 3.2 6.3 12.5 25 50 µg/ml Add growth medium  Add dilutions of test compound Inoculate & incubate cultures No drug: control MIC
Inoculate small samples on drug-free plates Minimum cidal concentration: the lowest concentration of an antimicrobial compound that kills a microbe  in vitro  Incubate plates Minimal inhibitory concentration: the lowest concentration of a antimicrobial compound that prevents growth of a microbe  in vitro 0.05 0.1 0.2 0.4 0.8 1.6 3.2 6.3 12.5 25 50
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Mechanisms of antibacterial action DNA mRNA ribosomes THF DHF pABA 50S 30S 50S 30S 50S 30S folate synthesis sulphonamides trimethoprim DNA topoisomerases quinolones, novobiocin RNA polymerase rifampicin  cell membrane polymyxins protein synthesis (30S) tetracyclines aminoglycosides fusidic acid and others protein synthesis (50S) macrolides lincosamides chloramphenicol oxazolidinones cell wall  -lactams vancomycin bacitracin
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 -lactams* inhibit this crosslinking   step *penicillins and cephalosporins
Inhibitors of peptidoglycan synthesis* D-ala—D-ala *steps shown are for Staphylococcus aureus
Action of  β -lactamase on penicillin. A number of bacteria, especially staphylococci, possess the enzyme  β -lactamase (penicillinase), which inactivates penicillin by cleavage of the  β -lactam ring at the point marked by the arrow
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[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object]
Cephalosporins ,[object Object]
First-Generation Cephalosporins: What do they cover? ,[object Object],[object Object],[object Object],[object Object],[object Object]
second generation cephalosporins ? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Third-Generation Cephalosporins ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Fourth generation cephalosporins ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Cell Wall Active Agents ,resistance problem ,[object Object],[object Object]
Group ii Inhibitors of protein synthesis ,[object Object],[object Object],[object Object],[object Object]
Inhibitors of protein synthesis ,[object Object],[object Object]
Inhibitors of protein synthesis ,[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
Group iii Nucleic Acid Synthesis Inhibition ,[object Object],[object Object]
Inhibitors of nucleic acid synthesis group iii (cont.) ,[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
Inhibitors of nucleic acid synthesis ,[object Object],[object Object],[object Object],[object Object]
single bacterial chromosome Topoisomerase inhibitors DNA gyrase RNA core RNA core quinolones
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
Mechanism of action of  TMP-SMX (sulfur drugs)
Sulphonamides: inhibitors of folate synthesis p -aminobenzoic acid + pteridine dihydropteroate synthase dihydropteroic acid dihydrofolic acid tetrahydrofolic acid sulphonamides trimethoprim
Inhibitors of metabolic pathways group v contd-- ,[object Object],[object Object],[object Object]
Targets of antibacterial agents ,[object Object],[object Object],[object Object],[object Object],[object Object]
Mechanisms of antimicrobial resistance 1. inactivate antimicrobial molecule e.g.   -lactamases: produced by many G+ and G– bacteria genes for   -lactamases often carried on plasmids, so easily spread between bacteria 2. alter antimicrobial target specific mutations in genes encoding target proteins can cause resistance without loss of target’s function 3. prevent access of antimicrobial to target e.g. reductions in permeability to drug (porins) drug efflux mechanisms — multi-drug resistance pumps 4. overexpress antimicrobial target 5. use alternative pathways to the one including the target
Spread of antimicrobial resistance transposon mobile genetic element carrying a drug resistance gene expressed from its own promoter: hops from chromosome to plasmid drug resistance plasmids can carry more than one drug resistance-encoding gene easily transferred between organisms integrons groups of drug resistance genes in a large array, under control of a single promoter responsible for rapid spread in Gram-positive bacteria

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Antimicrobial alpana

  • 1. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY BY: DR ALPANA VERMA Head, Department of Microbiology and Parasitology
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  • 21. Measurement of antimicrobial activity Minimal inhibitory concentration: the lowest concentration of an antimicrobial compound that prevents growth of a microbe in vitro 0.05 0.1 0.2 0.4 0.8 1.6 3.2 6.3 12.5 25 50 µg/ml Add growth medium Add dilutions of test compound Inoculate & incubate cultures No drug: control MIC
  • 22. Inoculate small samples on drug-free plates Minimum cidal concentration: the lowest concentration of an antimicrobial compound that kills a microbe in vitro Incubate plates Minimal inhibitory concentration: the lowest concentration of a antimicrobial compound that prevents growth of a microbe in vitro 0.05 0.1 0.2 0.4 0.8 1.6 3.2 6.3 12.5 25 50
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  • 34. Mechanisms of antibacterial action DNA mRNA ribosomes THF DHF pABA 50S 30S 50S 30S 50S 30S folate synthesis sulphonamides trimethoprim DNA topoisomerases quinolones, novobiocin RNA polymerase rifampicin cell membrane polymyxins protein synthesis (30S) tetracyclines aminoglycosides fusidic acid and others protein synthesis (50S) macrolides lincosamides chloramphenicol oxazolidinones cell wall  -lactams vancomycin bacitracin
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  • 43.  -lactams* inhibit this crosslinking step *penicillins and cephalosporins
  • 44. Inhibitors of peptidoglycan synthesis* D-ala—D-ala *steps shown are for Staphylococcus aureus
  • 45.
  • 46. Action of β -lactamase on penicillin. A number of bacteria, especially staphylococci, possess the enzyme β -lactamase (penicillinase), which inactivates penicillin by cleavage of the β -lactam ring at the point marked by the arrow
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  • 70. single bacterial chromosome Topoisomerase inhibitors DNA gyrase RNA core RNA core quinolones
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  • 77. Mechanism of action of TMP-SMX (sulfur drugs)
  • 78. Sulphonamides: inhibitors of folate synthesis p -aminobenzoic acid + pteridine dihydropteroate synthase dihydropteroic acid dihydrofolic acid tetrahydrofolic acid sulphonamides trimethoprim
  • 79.
  • 80.
  • 81. Mechanisms of antimicrobial resistance 1. inactivate antimicrobial molecule e.g.  -lactamases: produced by many G+ and G– bacteria genes for  -lactamases often carried on plasmids, so easily spread between bacteria 2. alter antimicrobial target specific mutations in genes encoding target proteins can cause resistance without loss of target’s function 3. prevent access of antimicrobial to target e.g. reductions in permeability to drug (porins) drug efflux mechanisms — multi-drug resistance pumps 4. overexpress antimicrobial target 5. use alternative pathways to the one including the target
  • 82. Spread of antimicrobial resistance transposon mobile genetic element carrying a drug resistance gene expressed from its own promoter: hops from chromosome to plasmid drug resistance plasmids can carry more than one drug resistance-encoding gene easily transferred between organisms integrons groups of drug resistance genes in a large array, under control of a single promoter responsible for rapid spread in Gram-positive bacteria