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8/14/2019 BIO 205 Chapter 24 Powerpoint
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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