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    BIO 205

    Chapter 24

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    Alexander Flemings Serendipitous Discovery of PenicillinUshered in the Era of Antibiotics

    Penicillium mold produces a substance that kills gram-positive

    bacteria

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    Selective toxicity means that a drug should harm the pathogen but not thehost

    The toxic dose of a drug is the concentration causing harm to the host

    The therapeutic dose is the concentration eliminating pathogens in thehost

    Together, the toxic and therapeutic doses are used to formulate thechemotherapeutic index

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    The Synthetic Antibacterial Agents

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    Sulfanilamide and Other Sulfonamides Target SpecificMetabolic Reactions

    Sulfonamides out compete essential folic acid components

    for binding sites in a bacterial enzyme

    They prevent nucleic acid synthesis and DNA replication

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    Other Synthetic Antimicrobials Have Additional Bacterial CellTargets

    Isoniazid interferes with cell wall synthesis in species of

    Mycobacterium

    Quinolones block DNA synthesis in bacteria

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    The Beta-Lactam Family of Antibiotics

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    Penicillin Has Remained the Most Widely Used Antibiotic

    Penicillins are active against many gram-positive andsome gram-negative bacteria

    They interfere with cell wall synthesis, causing the cell toburst

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    Some individuals experience an anaphylactic allergic reaction

    Many penicillin-resistant species produce beta-lactamasesthat inactivate penicillin

    Numerous semisynthetic penicillins have been developed

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    Other Beta-Lactam Antibiotics Also Inhibit Cell Wall Synthesis

    Cephalosporins are broader spectrum alternatives topenicillins

    Monobactams are active against aerobic, gram-negative rods

    Carbapenems are broad spectum drugsFor example, Imipenem

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    Vancomycin Also Inhibits Cell Wall Synthesis

    It is effective against gram-positive bacteria such asstaphylococci

    Side effects include damage to the ears and kidneys

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    Chloramphenicol is used against a wise variety of bacteria

    and some rickettsiae and fungi

    It is reserved for serious infections like:

    meningitis

    choleratyphoid and typhus feversRocky Mountain spotted fever

    Severe side effects include aplastic anemia and gray

    syndrome

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    Tetracyclines have a similar antimicrobial range tochloramphenicol

    They have a benzene ring formation

    They can destroy intestinal microbiota and cause stainingof the teeth

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    Some Antibiotics Inhibit Nucleic Acid Synthesis

    Rifampin interferes with RNA synthesis

    It is effective against tuberculosis, leprosy, andmeningitis

    It can cause liver damage

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    Targets for antibacterial agents

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    Antibiotic Assays and Resistance

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    The agar disk diffusion method involves different antibioticsdiffusing from paper disks in a bacterial colony

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    There Are Four Mechanisms of Antibiotic Resistance

    Many species of bacteria have evolved resistance to certainantibiotics and synthetic agents

    The evolution of strains ofS. aureus resistant to multiple drugs isparticularly alarming

    1. Resistance to sulfonamides may develop if the bacterialenzyme changes or if the bacteria evolves an alternate

    metabolic pathway

    3. Bacteria may evolve the ability to enzymatically inactivate anantibiotic

    5. Bacteria may evolve the ability to prevent drug entry into thecytoplasm or to pump the drug out of the cytoplasm

    7. Bacteria can evolve changes in drug targets like ribosomesor enzymes involved in replication

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    Unnecessarily large antibiotic doses allow resistant strains toovergrow susceptible ones

    If resistant strains spread to other patients, a superinfectionoccurs

    Antibiotics are available over the counter in developing

    countries, allowing for overuse and incorrect use

    Antibiotic use is widespread in livestock feeds

    They can be transmitted to humans through meat

    consumption

    Bacterial cells can pass resistance genes to other bacterialcells

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    New Approaches to Antibiotic Therapy Are Needed

    Scientists work to find new antibiotic targets in pathogens

    The lipopolysaccharide in gram-negative membranescontains several possible targets

    Interference with DNA adenine methylase disables:DNA structurereplicationrepair

    Discovery of new and unique antibiotics is necessary

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    End of Chapter 24