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OPTO435 Microbiology II Gamal El-Hiti

Discover the history, mode of action, and importance of antibiotics in treating microbial infections. Learn about the different types of antibiotics and how they target specific bacterial processes. Explore the challenges of treating Gram-negative bacteria and the development of resistance.

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OPTO435 Microbiology II Gamal El-Hiti

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  1. OPTO435 Microbiology II Gamal El-Hiti

  2. Antimicrobial Drugs Lecture Two

  3. Learning Outcomes OPT435 L02 – W02

  4. Antibiotics Chemotherapy is the use a drug (chemical) to treat a disease due to a microbial infection. Antibiotic drugs interfere with the growth of microbes within a host. Antibiotics are of biological origin and produced by microbes to inhibit others. They can be used to treat microbial infections. Chemotherapeutic agents (antibiotics) are synthesized drugs or chemically modified biological products. OPT435 L02 – W02

  5. Antibiotics  Why is it more difficult to treat Gram-negative bacteria in comparison to Gram-positive bacteria?  Resistance against antibiotics is more common in Gram-negative bacteria due to the presence of external membrane covering the cell wall, but this membrane is absent in Gram-positive bacteria.  Gram-negative bacteria have channels that can prevent the entry of antibiotics.  Also, the channels can expel out antibiotics. OPT435 L02 – W02

  6. Antibiotics  Gram-positive bacteria produce exotoxins, but Gram-negative bacteria produce exotoxins and endotoxins. OPT435 L02 – W02

  7. Antibiotics OPT435 L02 – W02

  8. History of Antibiotics  Salvarsan (arsphenamine) was synthesized by Paul Ehrlich in 1907 and was introduced by Sahachiro Hata as the first effective treatment of syphilis in 1910.  The concept of chemotherapy to treat microbial diseases was born.  Fleming discovered penicillin in 1928.  Sulfa drugs (sulfanilamide) were discovered in 1932 against Gram + bacteria.  Howard Florey and Ernst Chain performed the first clinical trial of penicillin in 1940. OPT435 L02 – W02

  9. History of Antibiotics  Selective toxicity  Antimicrobial drugs are chemicals that have selective toxicity against microbes without damaging the host cells.  Therapeutic index  The ratio between the toxic dose and the therapeutic dose or ratio of the median lethal dose (LD50) to median effective dose (ED50).  LD50 is the quantity of a drug that kills 50% of the test sample. OPT435 L02 – W02

  10. Antibiotics Mode of Action  ED50is the dose that produces the desired effect within 50% of a population.  High therapeutic index means less toxic.  Antibiotics action  Different antibiotics have different mode of action depending on their structures and degree of affinity to certain target sites within the bacterial cells. Inhibitors for cell wall synthesis Humans and animals cells do not have cell walls. OPT435 L02 – W02

  11. Antibiotics Mode of Action A drug that targets cell walls can selectively kill or inhibit bacterial organisms. Inhibitors for cell membrane function Cell membranes are important barriers that regulate the flow of substances. Membranes disruption could result in leakage of solutes needed for cell’s survival. Inhibitors for protein synthesis Enzymes are primarily made of proteins. Protein is necessary for the multiplication of all bacterial cells. OPT435 L02 – W02

  12. Antibiotics Mode of Action Several types of antibacterial agents bind to either 30S or 50S subunits of ribosomes. This activity leads to death of organism. Inhibitors for nucleic acid synthesis DNA and RNA are keys to the replication. Some antibiotics compromise bacterial multiplication and survival. Inhibitors for other metabolic processes e.g.Disruption of folic acid pathway, which is a necessary step for bacteria to produce precursors for DNA synthesis. OPT435 L02 – W02

  13. Penicillin (-lactams) OPT435 L02 – W02

  14. Penicillin (-lactams) OPT435 L02 – W02

  15. Penicillin (-lactams)  Penicillin is a group of antibiotics.  Natural and semisynthetic penicillins contain β-lactam ring.  Natural penicillins produced by Penicilliumare effective against Gram positive cocci and spirochetes.  Semisynthetic penicillins can be made in laboratory by adding different side chains into the β-lactam ring.  Penicillins are still widely used today, but many bacteria have now become resistant. OPT435 L02 – W02

  16. Penicillin (-lactams)  Bacteria that attempt to grow and divide in the presence of penicillin fail to do so.  Bacteria end up shedding their cell walls. OPT435 L02 – W02

  17. Penicillin (-lactams)  Bacteria are constantly remodel their peptidoglycan cell walls.  They build and break down portions of the cell wall as they grow and divide.  β-Lactam antibiotics inhibit the formation of peptidoglycan cross-links by binding to the enzyme DD-transpeptidase.  As a consequence, DD-transpeptidase cannot catalyse formation of these cross-links, causing the cell to rapidly die.  If you are allergic to penicillin, tell the doctor. OPT435 L02 – W02

  18. Penicillin (-lactams) OPT435 L02 – W02

  19. Penicillin (-lactams)  Penicillinase (β-lactamase)  Bacterial enzyme that destroys natural penicillins.  Penicillinase resistant penicillins  Methicillin replaced by oxacillin and nafcillin due to methicillin-resistant Staphylococcus aureus (MRSA).  Extended-spectrum penicillins  Ampicillin, amoxicillin, carboxypenicillins and ureidopenicillins (also good against Pseudomonas aeruginosa). OPT435 L02 – W02

  20. Penicillin (-lactams) OPT435 L02 – W02

  21. Cephalosporins (-lactams)  The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium.  More stable to bacterial β-lactamases than penicillin.  Broader spectrum to be used against penicillin-resistant strains.  Structure and mode of action resembles penicillin. OPT435 L02 – W02

  22. Vancomycin (glycopeptides)  Vancomycin recognizes and binds to the two D-ala residues on the end of the peptide chains. However, in resistant bacteria, the last D-ala residue has been replaced by a D-lactate, so vancomycin cannot bind. OPT435 L02 – W02

  23. Vancomycin (glycopeptides) •  Used to kill Methicillin-resistantStaphylococcus aureus (MRSA) which is a bacterium responsible for several difficult-to-treat infections in humans. •  Inhibition of cell wall synthesis. OPT435 L02 – W02

  24. Other Antibiotics OPT435 L02 – W02

  25. Antibiotics and Normal Flora •  Antibiotics act only against bacteria and are ineffective against viral infections caused by viruses. •  Research on antibiotics showed that taking even a single regimen of antibiotics (i.e. about 10 days) makes a person 3 to 4 times more likely to get another infection. •  This is because antibiotics often kill off too many of the host’s inherent beneficial flora leaving the host even more unprotected against new infectious agents. OPT435 L02 – W02

  26. Kirby-Bauer Test  Kirby-Bauer antibiotic testing  It is a disk diffusion antibiotic sensitivity testing.  It is a test which uses antibiotic-impregnated wafers to test whether particular bacteria are susceptible to specific antibiotics.  White wafers containingantibiotics are placed on aplate of bacteria. OPT435 L02 – W02

  27. Kirby-Bauer Test  Circles of poor bacterial growth surround some wafers indicating susceptibility to the antibiotic. OPT435 L02 – W02

  28. Antibiotic Resistance •  Bacteria can develop resistance to antibiotics by mutating existing genes, or by acquiring new genes from other strains. •  A variety of mutations can lead to antibiotic resistance. •  Mechanisms of antibiotic resistance •  Enzymatic destruction of drug •  Prevention of penetration of drug •  Alteration of drug's target site •  Rapid ejection of the drug OPT435 L02 – W02

  29. Antibiotic Resistance OPT435 L02 – W02

  30. Antibiotic Resistance •  Misuse of antibiotics selects for resistance mutants. •  Misuse of antibiotics includes one or more of the following: •  Using outdated or weakened antibiotics. •  Using antibiotics for the common cold and other inappropriate conditions. •  Using antibiotics in animal feed. •  Failing to complete the prescribed regimen. •  Using someone else's leftover prescription. OPT435 L02 – W02

  31. Antibiotic Resistance OPT435 L02 – W02

  32. Antifungal Drugs •  Antifungal is a pharmaceutical fungicide used to treat mycoses such as athlete's foot and ringworm. •  Polyene antifungals •  It has multiple conjugated double bonds. OPT435 L02 – W02

  33. Antifungal Drugs •  Polyene antifungals •  It bind with sterols in the fungal cell membrane (Inhibition of ergosterol). OPT435 L02 – W02

  34. Antiparasitic Drugs •  Antiparasitics are medications that can be used to treat parasitic diseases. •  The empiric use of cinchona-bark to treat parasitic diseases began in the 17th century. •  The isolation of the alkaloid quinine was isolated in 1820. •  Early antiparasitics were ineffective, frequently toxic to patients and difficult to administer due to the difficultyin distinguishing between host and parasite. OPT435 L02 – W02

  35. Antiparasitic Drugs •  Diethylcarbamazine is used in the treatment of certain worm infections. •  This medicine works by killing the worms. •  It can not kill pinworms or tapeworms. •  It is not expected that diethylcarbamazine will cause different side effects or problems in children than it does in adults. OPT435 L02 – W02

  36. AntiviralDrugs •  Antiviral drugs are a class of medication that used specifically for treating viral infections caused by viruses. •  Like antibiotics specific antivirals are used for specific viruses. •  Unlike most antibiotics, antiviral drugs can not destroy their target pathogen without destroying the host cells. •  They inhibit the viruses development. •  Highly active antiretroviral therapies HAART) is used to treat virial infections. OPT435 L02 – W02

  37. AntiviralDrugs •  Designing safe and effective antiviral drugs is difficult, because viruses use the host's cells to replicate. •  This makes it difficult to find targets for the drug that would interfere with the virus cells without harming the host organism's cells. •  Moreover, the major difficulty in the development and manufacture of vaccines and new antiviral drugs is due to the viral variation. OPT435 L02 – W02

  38. AntiviralDrugs  Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are antiretroviral drugs used in the treatment of human immunodeficiency virus (HIV).  NNRTIs inhibit reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of HIV.  RT is one of the most popular targets in the field of antiretroviral drug development.  Some progress has been made with NNRTIs. OPT435 L02 – W02

  39. AntiviralDrugs  Acyclovir  Is a guanosine analogue antiviral drug.  Ii inhibits DNA synthesis.  Inhibition of herpes virus replication and treatment of chickenpox and shingles.  OPT435 L02 – W02

  40. AntiviralDrugs OPT435 L02 – W02

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