1/26/2016 Antimicrobial drugs act by inhibiting or Microbes interfering with the growth of microbes. .Antimicrobial drugs act within the host without damaging the host. Invisible Invaders Antibiotics are one of the most important Amazing Allies discoveries of modern medicine. Resistance to antibiotics poses a "major global threat"to public health according to WHO. Chapter 20 Antimicrobial Drugs The History of Chemotherapy The History of Chemotherapy x:selectively finding and Learning Objectives stroying pathogens without damaging the host Identify the contributions of Paul Ehrlich and the use of chemicals to Alexander Fleming to chemotherapy. Name the microbes that produce most Antibiotic:a substance produced by a antibiotics. microbe that,in small amounts,inhibits another microbe microbes
1/26/2016 1 Invisible Invaders Amazing Allies Chapter 20 Antimicrobial Drugs • Antimicrobial drugs act by inhibiting or interfering with the growth of microbes. • Antimicrobial drugs act within the host without damaging the host. • Antibiotics are one of the most important discoveries of modern medicine. • Resistance to antibiotics poses a "major global threat" to public health according to WHO. Pseudomonas aeruginosa resistant to many antibiotics The History of Chemotherapy Learning Objectives Identify the contributions of Paul Ehrlich and Alexander Fleming to chemotherapy. Name the microbes that produce most antibiotics. The History of Chemotherapy • Selective toxicity: selectively finding and destroying pathogens without damaging the host • Chemotherapy: the use of chemicals to treat a disease • Antibiotic: a substance produced by a microbe that, in small amounts, inhibits another microbe • Antimicrobial drugs: synthetic substances that interfere with the growth of microbes
1/26/2016 The History of Chemotherapy The History of Chemotherapy ·8ec8ee8￥Y .1928:Fleming discovered penicillin, Ehrlich,Germany produced by Penicillium ·be8 oul e 1932:Prontosil red dye used for streptococcal infections horr pathager but 1940:First clinical trials of penicillin Father of chemotherapy Today there is a growing problem of antibiotic resistance %gea25米t "One sometimes finds what one is ·Nobel prize in1908 ot looking for." Alexander Fleming TABLE 20.7 Representative Sources of Antibiotics cieifn8m5mbncsie2alteiera Microorganism Antibiotic GRAM-POSITIVE RODS Most commonly Streptomyces species B联nan Polymyrin ACTINOMYCETES FUNGI
1/26/2016 2 The History of Chemotherapy • Birth of modern chemotherapy is credited to the efforts of Paul Ehrlich, Germany • He speculated about a “magic bullet” that would selectively target and destroy pathogens but not harm the host. • Father of chemotherapy • Made the first magic bullet Salvarsan to treat syphilis • Nobel prize in 1908 The History of Chemotherapy • 1928: Fleming discovered penicillin, produced by Penicillium • 1932: P t sil d d s d f 1932: Prontosil red dye used for streptococcal infections • 1940: First clinical trials of penicillin • Today there is a growing problem of antibiotic resistance Microbes from natural environments (soil) will show bacterial inhibition by antibiotics produced by bacteria Most commonly Streptomyces species
1/26/2016 Spectrum of Antimicrobial Activity Spectrum of Antimicrobial Activity Selective toxicity has Learning Objectives numerous fargets for drug development for prokaryotes Describe the problems of chemotherapy for viral,fungal,protozoan,and helminthic Cell structure of eukaryotes infections. is very similar to that of the human host Define the following terms:spectrum of activity,broad-spectrum antibiotic, Viruses multiply within the Superinfection. host cell. Selective toxicity is more difficult for viruses and eukaryotic pathogens. The Spectrum of Activity of Antibiotics and Other Antimicrobial Drugs Spectrum of Antimicrobial Activity Narrow spectrum of microbial activity:drugs that affect a narrow range of microbial types Antibiotics target the normal flora as well as the pathogen. tive bacteria Survivors may flourish and become opportuntistic pathogens due to overgrowth. Superinfection:overgrowth of normal microbiota that is resistant to antibiotics
1/26/2016 3 Spectrum of Antimicrobial Activity Learning Objectives Describe the problems of chemotherapy for viral, fungal, protozoan, and helminthic infections. Define the following terms: spectrum of activity, broad-spectrum antibiotic, superinfection. Spectrum of Antimicrobial Activity • Selective toxicity has numerous targets for drug d l t f k t development for prokaryotes • Cell structure of eukaryotes is very similar to that of the human host • Viruses multip yl within the host cell. • Selective toxicity is more difficult for viruses and eukaryotic pathogens. The Spectrum of Activity of Antibiotics and Other Antimicrobial Drugs • Narrow spectrum of microbial activity: drugs that affect a narrow range of microbial types • B d roa -spect tibi ti trum antibiotics: aff t b d f ffect a broad range of gram-positive or gram-negative bacteria Spectrum of Antimicrobial Activity • Antibiotics target the normal flora as well as the p g atho en. • Survivors may flourish and become opportuntistic pathogens due to overgrowth. • Superinfection: overgrowth of normal mi bi h i i icrobiota that is resistant to antibiotics
1/26/2016 The Action of Antimicrobial Drugs The Action of Antimicrobial Drugs ·Bactericidal Learning Objective -Kill microbes directly Identify five modes of action of antimicrobial Bacteriostatic drugs. -Prevent microbes from growing -Host's immune system usually kills the pathogen Five Major Targets of Antibacterial Drugs Antimicrobial drugs target essential functions of the microbe The Action of Antimicrobial Drugs Inhibiting cell wall synthesis -Peptidoglycan is found only in bacterial cell walls. -Penicillins prevent the synthesis of peptidoglycan -Cell wall is weakened and undergoes lysis. ma embran
1/26/2016 4 The Action of Antimicrobial Drugs L arn ng O j ct earning Objective Identify five modes of action of antimicrobial drugs. The Action of Antimicrobial Drugs • Bactericidal – Kill microbes directly • Bacteriostatic – Prevent microbes from growing – Host’s immune system usually kills the pathogen Five Major Targets of Antibacterial Drugs Antimicrobial drugs target essential functions of the microbe. The Action of Antimicrobial Drugs • Inhibiting cell wall synthesis – Peptidoglycan is found only in bacterial cell walls. – Penicillins prevent the synthesis of peptidoglycan – Cell wall is weakened and undergoes lysis
1/26/2016 Inhibition of bacterial cell wall synthesis by The Action of Antimicrobial Drugs penicillin Inhibiting protein synthesis -Target bacterial 70S ribosomes -Eukaryotes have 805 ribosomes -Difference in ribosome structure accounts for selective toxicity -However,mitochondria have 705 ribosomes 四1m The ba so some toxicity may occur -Chloramphenicol,erythromycin, streptomycin,tetracyclines Protein synthesis Inhibition of protein synthesis by antibiotics. Growing polypeptide nthesis nd inhibits site -Protein synthesis site ortse Totracyclines hh8r2e8s305ay nges shape of Interfere with Translation RNA to mRNA- bosome comple
1/26/2016 5 Inhibition of bacterial cell wall synthesis by penicillin The Action of Antimicrobial Drugs • Inhibiting protein synthesis – Target bacterial 70S ribosomes – Eukaryotes have 80S ribosomes – Difference in ribosome structure accounts for selective toxicity – However, mitochondria have 70S ribosomes so t i it some toxicit y may occur – Chloramphenicol, erythromycin, streptomycin, tetracyclines Protein synthesis Protein synthesis site Growing polypeptide Tunnel 5' 50S 30S mRNA 3' Three-dimensional detail of the protein synthesis site showing the 30S and 50S subunit portions of the 70S prokaryotic ribosome Inhibition of protein synthesis by antibiotics. Growing polypeptide 50S Chloramphenicol Binds to 50S portion and inhibits formation of tid b d Messenger RNA 50S portion tRNA Protein synthesis site peptide bond RNA Streptomycin Changes shape of 30S portion, causing code on mRNA to be read incorrectly 70S prokaryotic ribosome Translation 30S portion Direction of ribosome movement Tetracyclines Interfere with attachment of tRNA to mRNA– ribosome complex