Slides_Antibiotics_1

Slides_Antibiotics_1 - The History of Medicine 2000 B.C....

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Unformatted text preview: The History of Medicine 2000 B.C. – Here, eat this root. 1000 A.D. – That root is heathen. Here, say this prayer. 1850 A.D. – That prayer is superstition. Here, drink this potion. 1920 A.D. – That potion is snake oil. Here, swallow this pill. 1945 A.D. – That pill is ineffective. Here, take this penicillin. 1955 A.D. – Oops…bugs mutated. Here, take this tetracycline. 1960-1999 – 39 more “oops”. Here, take this more powerful antibiotic. 2000 A.D. – The bugs have won! Here, eat this root. -Anonymous (WHO, 2000) Antibiotic Sulfonamides Penicillin Streptomycin Chloramphenicol Tetracycline Erythromycin Vancomycin Methicillin Ampicillin Cephalosporins Year Deployed 1 930s 1 943 1 943 1 947 1 948 1 952 1 956 1 960 1 961 1 960s Resistance Observed 1 940s 1 946 1 959 1 959 1 953 1 988 1 988 1 961 1 973 late 1 960s Outline •  •  •  •  Defining Antibiotics Mechanism of Action Mechanism of Resistance Acquiring Resistance Basic of Antibiotics •  •  •  •  Either bacteriostatic or bactericidal MIC – minimum inhibitory concentration Minimum toxicity to mammalian cells Antibiotic reaches a slightly higher concentration in serum or tissues than the MIC Antibiotic Targets Figure 20.14 Cell Wall Biosynthesis Ribosome Topoisomerase Mechanism of ABX Resistance •  Innate mechanisms –  Outermembrane –  Biofilm formation •  Specific mechanisms –  ABX export –  Modify the target of the ABX –  Modify the ABX Outermembrane •  The presence of an outermembrane (Gram-negative versus Gram-positive) •  Pore size differences Hancock RE. Clin Infect Dis. 1998 Aug;27 Suppl 1:S93-9 Biofilm Formation For more info: http://www.dartmouth.edu/~gotoole/antibiot.html Multidrug Efflux Pumps Modifying the Target Changes to the ribosome http://www.weizmann.ac.il/sb/ faculty_pages/Yonath/14A.jpg Modifying the ABX Gene Shuffling recombination between dissimilar genes to create new recombinant genes Conant GC, Wagner A. Genome Biol. 2005;6(6):R50 PBP Resistant to Methicillin Crystal structure of the transpeptidase domain of R6-PBP2x (17) Carapito, R. et al. J. Biol. Chem. 2006;281:1771-1777 1=size markers 2=VRE 3=MRSA 4=VRSA Part B= southern blot with vanA gene that encodes vancomycin resistance in VRE Fig. 1. Restriction analysis of pLW1043 and localization of vanA by Southern hybridization. (A) Isolated plasmids were digested with HindIII, and the resulting fragments were separated on an agarose gel and stained with ethidium bromide. Lane 1, molecular size marker; lane 2, VRE plasmids; lane 3, pAM829 (MRSA); lane 4, pLW1043 (VRSA). (B) DNA fragments from the gel were transferred to nitrocellulose and hybridized with a probe for vanA. Lane numbers in (B) correspond to those in (A). VRE have transposon(Tn; Red) that has gene for high level vancomycin resistance. This Tn is on a conjugative plasmid that replicates in VRE. This VRE conjugative plasmid can be transferred to S. aureus, but this plasmid does not replicate in S. aureus. It appears that the Tn from the VRE plasmid hopped onto the MRSA plasmid resulting in VRSA. This MRSA plasmid is a conjugative plasmid. ...
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This note was uploaded on 03/06/2012 for the course MIMG 100 taught by Professor Lazazzera during the Summer '10 term at UCLA.

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