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1、A NEW SUPERBACTERIA, IMMUNE TO MOST ANTIBIOTICS, FOUND SPREADING FAST,What is an antibiotic? http:/ antibacterial substances produced by microorganisms Semi-synthetic derivatives of natural antibiotics What are some sources of natural antibiotics? Molds e.g., penicillin G from Penicillium notatum Ba
2、cteria e.g. tetracycline from Streptomyces speciesSome examples of semi-synthetic antibiotics Penicillin “family” - methicillin, ampicillin, oxycillin Doxycycline is a semi-synthetic tetracycline,What are some typical “targets” of some common antibiotics?,Cell walls peptidoglycans - penicillin Ribos
3、omes - tetracycline DNA replication enzymes (e.g., DNA gyrase) ciprofloxacin (“cipro”) What is DNA gyrase? Unwinds dsDNA to allow access to single-stranded template for DNA replicationHow do bacteria resist antibiotics?,Cell wall and antibiotics,Cell wall is an important antibiotic target Todors Onl
4、ine Textbook of Bacteriology: Antimicrobial Agents in the Treatment of Infectious Disease (page 3) http:/ (scroll down to “Cell wall synthesis inhibitors”),Structure and Function,Cell Wall Todors Online Textbook of Bacteriology: Structure and Function of Bacterial cells (page 5 only) Http:/ - impart
5、s some rigidity Sugar backbone - NAG & NAMA (Human lysozyme cleaves (1,4) bond) Amino acid cross links adds rigidity Peptidoglycan layer thickness,Cell wall and antibiotics,Cell wall is an important antibiotic target Todors Online Textbook of Bacteriology: Antimicrobial Agents in the Treatment of In
6、fectious Disease (page 3) http:/ (scroll down to “Cell wall synthesis inhibitors”)Penicillin (produced by Penicillium notatum fungus) Penicillin binds to transpeptidases - cannot function Prevents cross-linking of peptide chains between adjacent sugar backbones Cell wall synthesis does not occur Rep
7、licating bacterial cells cannot survive Bacterial cell wall components are NOT found anywhere in humans Penicillin will not harm humans (except for allergic reactions),Penicillin resistance,Todors Online Textbook of Bacteriology: Bacterial Resistance to Antibiotics (page 3) http:/ structure beta-lac
8、tam ring Beta-lactamase produced by bacteria disrupts beta-lactam ring Penicillin is rendered inactive (can not bind to transpeptidases) Cell wall synthesis is normal (bacterium is resisting the antibiotics affect),Methicillin - responding to penicillin resistance,Methicillin (“semi-synthetic” penic
9、illin) Methicillin also interferes with transpeptidases Penicillin “family” all have same beta-lactam ring Differ in the side chain N-acyl group Methicillin and other semi-synthetic penicillins are resistant to beta-lactamase Bacteria cannot inactive methicillin using beta-lactamase,Methicillin resi
10、stance,Some bacteria can alter their transpeptidases Still function to cross-link peptidoglycan sugar backbones Not affected by any of the penicillins Methicillin-resistant Staphylococcus aureus (MRSA),Vancomycin responding to methicillin resistance,Vancomycin is not a member of the penicillin famil
11、y Thus not affected in any way by beta-lactamase Does not act by interfering with transpeptidases So not affected by any change in transpeptidases Acts by binding to D-alanines at ends of peptides Prevents cross-linking Effective against gram-positive, but not gram-negative bacteria Outer membrane o
12、f gram-negative bacteria prevents “penetration” of vancomycin into the cell wall area,Vancomycin resistance,Bacteria substitute another amino acid for D-alanine (e.g., D-serine) Vancomycin cannot bind to that other amino acid Does not interfere with cross-linking,D-Ser,D-Ser,Many more antibiotics ex
13、ist to treat bacteria that have developed resistance to the “common” antibiotics http:/ (Scroll down to “Classes of Antibiotics and their Properties“)Resistance continues to develop against a growing list of these available antibioticsNew antibiotics continue to be developedBacteria continue to deve
14、lop additional resistance“The race is on” Bacteria vs. the antibiotics,“Superbacteria”,A NEW SUPERBACTERIA, IMMUNE TO MOST ANTIBIOTICS, FOUND SPREADING FAST Appear to be resistant to “every antibiotic known to man” (quote from the news media) probably a little media “hype” MRSA Methicillin-resistant
15、 Staphylococcus aureus “Flesh-eating bacteria” highly virulent form of Streptococcus pyogenesThe “Superbacteria” in the article is more likely resistant to all of the “common” antibiotics (penicillin family)Antibiotics that affect bacterial cell walls are still the first choice No cell walls in huma
16、n cells Relatively inexpensive (compared to antibiotics with other “targets”),TWO Clicker questions at the start of class,1. Autoclaving and its consumer equivalent, pressure cooking, are methods designed to destroy which one of the following components of bacterial cells? Hint: these components are
17、 most often found in members of the two genera, Clostridium and Bacillus.2. Although many antibiotics affect bacterial cell walls (the most desirable “target”), quite a few commercially available antibiotics affect other components of bacterial cells. Although these other antibiotics are more risky,
18、 as the bacterial cell “targets” are often similar to human cell components, they are still employed when dealing with various antibiotic-resistant bacteria. For example, which one of the following antibiotics has a unique bacterial DNA gyrase as its target?Powerpoint slide added (High frequency recombination) COPIES are on ends of tables in the classroom,
