Sale!

Microbiology An Evolving Science 2nd Edition Slonczewski Foster Test Bank

$80.00 $12.99

Microbiology An Evolving Science 2nd Edition Slonczewski Foster Test Bank

ISBN-13: 978-0393934472

ISBN-10: 0393934470

 

 

Description

Microbiology An Evolving Science 2nd Edition Slonczewski Foster Test Bank

ISBN-13: 978-0393934472

ISBN-10: 0393934470

 

 

 

 

Be the best nurse you can be:

Nursing test banks are legit and very helpful. This test bank on this page can be downloaded immediately after you checkout today.

Here is the definition of nursing

Its true that you will receive the entire legit test bank for this book and it can happen today regardless if its day or night. We have made the process automatic for you so that you don’t have to wait.

We encourage you to purchase from only a trustworthy provider:

Our site is one of the most confidential websites on the internet. We maintain no logs and guarantee it. Our website is also encrypted with an SSL on the entire website which will show on your browser with a lock symbol. This means not a single person can view any information.

Have any comments or suggestions?

When you get your file today you will be able to open it on your device and start studying for your class right now.

Microbiology An Evolving Science 2nd Edition Slonczewski Foster Test BankRemember, this is a digital download that is automatically given to you after you checkout today.

Free Nursing Test Questions:

 

CHAPTER 27: Antimicrobial Chemotherapy

 

CONCEPT MAP

 

  1. Section 27.1 The Golden Age of Antibiotic Discovery
    1. Antibiotics—Greek word meaning “against life”; definition—compounds produced by one species of microbe that can kill or inhibit the growth of other microbes
      1. History: ancient remedies—made from soils and mold probably contained natural antibiotics
      2. Modern antibiotic revolution: began with Fleming’s rediscovery of penicillin in 1928; actual discovery of penicillin described by Duchesne in 1896
        1. Duchesne (French medical student): noticed saddle being kept in dark/damp conditions to encourage mold growth of saddles, helped reduce saddle sores on the horses; used mold to inject into diseased guinea pigs, all lived, work submitted to Pasteur Institute but ignored
        2. Fleming: mold-growth contaminate on an old petri dish of Staphylococcus aureas bacteria, area around mold growth had no bacterial growth; sample of the mold, Penicillin notatum, synthesized a chemical that diffused through the agar killing aureas colonies; presented findings, little interest due to the fact penicillin appeared to be an unstable molecule
        3. Florey and Chain (Oxford): rediscovered Pasteur’s work, purified penicillin, injected into diseased mice (Staphylococcus or Streptococcus infection), majority of mice survived; human trials followed and proved successful; won 1945 Nobel Prize in Medicine (shared with Pasteur)
  • Gerhard Domagk (German physician at the Bayer Institute) investigated antimicrobial compounds in the 1930s; daughter with serious streptococcal infection spreading to lymph nodes, amputation seemed necessary but instead he injected her with red dye (prontosil) that cleared infection completely; prontosil had not worked on agar media tests but had worked in mouse studies
    1. Prontosil needs to be metabolized by the body into another compound, sulfanilamide (an analog of para-aminobenzoic acid, PABA); stops PABA from being made into folic acid to make nucleic acid precursors; inhibits bacteria because they have to make folic acid; no affect on human cells because obtained through diet
    2. Controversy with in vivo testing of pathogens and antimicrobial agents in concentration camps during World War II
    3. Discovered first effective therapy for tuberculosis, thiosemicarbazones and isoniazid, still used
  1. Waksman (Rutgers): during 1930–1940s began screening 10,000 strains of soil bacteria and fungi for an ability to inhibit growth of kill bacteria; 1944 discovered streptomycin from Streptococcus griseus

 

  1. Section 27.2: Basic Concepts of Antimicrobial Therapy
    1. Selective toxicity—antibiotics must selectively kill or inhibit the pathogen but not the host
      1. Ehrlich: early 1900s, one of the first to realize that antimicrobial compounds would need to be “magic bullets” targeting pathogen only; experimented with Salvarsan (arsenical compound) found to exhibit selective toxicity in killing syphilis agent Treponema pallidum
      2. Selective toxicity possible because key aspects of a microbe’s physiology are different from eukaryotes (e.g.. cell wall structure/ penicillin, ribosome structure/ tetracyclines, etc.); when given in relatively low doses essentially invisible to host cells
  • Potential problems: some antibiotics when given at high doses can interact with eukaryote biology (e.g., chloramphenicol targets bacterial 50S ribosome interferes with bone marrow cell development causing aplastic anemia); toxicity can be age-dependent (e.g., tetracycline should not be given to children because it causes defects in human bone growth plates; development of allergies to the antibiotic that are worse than the infection itself
  1. Drug susceptibility—the susceptibility of the drug on a microbe versus drug sensitivity—the sensitivity of the host to the drug
  1. Spectrum of activity—the range of species affected by the antibiotic
    1. Antibiotic—refers to antimicrobials that affect bacteria; antifungal (affect fungus); antiprotozoan (affect protozoan), antiviral (affect viruses)
    2. Narrow range—penicillin primarily kills Gram-positive bacteria only; ampicillin, penicillin with an added amino group, can penetrate Gram-negative outer membrane increasing the spectrum of activity to both Gram-positives and Gram-negatives; extremely narrow range includes isoniazid, which only kills Mycobacterium tuberculosis
  • Broad-spectrum antibiotics can destroy normal flora as well as pathogen, disrupting our host–microbiota interactions and also provide a growth advantage for species that are resistant to the antibiotic
  1. Bacteriostatic—antibiotics that prevent bacterial growth; bacteriocidal—antibiotics that directly kill the target microbe

 

  • Section 27.3: Measuring Drug Susceptibility
    1. Several factors must be taken into consideration when treating an infection with antibiotics—relative effectiveness of different antibiotics on the organism causing infection (including possible drug resistance); average attainable tissue levels of each drug
    2. Minimal inhibitory concentration (MIC)—definition—the lowest concentration of the drug that will prevent the growth of an organism; tests in vitro effectiveness; MIC for one drug will differ among different bacterial species (g., drug may penetrate different organisms differently, target affinity may differ between different organisms)
      1. How test is performed: test tube series of broth with serially dilutions of antibiotic to be tested inoculated with specific bacteria at low, contact density and incubated overnight, examined for bacterial growth; tube with lowest concentration of drug that shows no growth is the MIC tube; test does not determine bacteriostatic or cidal
      2. Useful to test a single drug’s effectiveness against a single bacterial isolate; not good for multidrug screening due to time needed for the test
  • Quicker way, MIC Etest strip with gradient of concentrations with in a single test strip can be placed on an agar plate inoculated with dilute lawn of a specific bacteria; antibiotic diffuses out of strip into agar (higher concentration of drug travels farther creating large zone of inhibition); MIC point where the elliptical zone of inhibition intersects with the strip
  1. Zone of inhibition: definition: where the antibiotic has stopped bacterial growth

 

  1. Kirby-Bauer disk susceptibility test—test that uses a series of round-filter-paper disks impregnated with different antibiotics
    1. How test is performed: antibiotic disks can placed (up to 12 different disks per plate) on a agar plate with a bacterial lawn; incubation with disks allows diffusion of the antibiotic into the surrounding agar creating zone of inhibition of different widths depending upon: (1) type of antibiotic used, (2) concentration of the disk used, and (3) organisms susceptibility to the drug
    2. Diameter of zone correlates to MIC of the antibiotic by empirical correlation (i.e., each disk is impregnated with a standard concentration and every antibiotic has a quantifiable MIC for different bacterial species or strains); the outermost ring of the zone of inhibition is the MIC; a graph plotting MIC on one axis and zone diameter on other provides correlation
  • After incubation measurements of zones are compared with tables of susceptibility for the particular organism (zone sizes fall into one of three categories: Resistant, Intermediate, or Susceptible)
  1. Correlation of MIC with tissue levels—in order for a drug to be effective in vivo tissue concentration of the drug must remain above the MIC
    1. Things that affect antibiotic tissue concentration: kidney clearance and/or liver destruction; concentration of antibiotic must be kept at a sufficient level to be effective with minimal side effects (many drugs prescribed in doses,
      e.g., take 1 pill 4× a day)
  2. Kirby-Bauer is a standardized test—all labs perform the same way, making results reproducible
    1. Laboratory standardizations include
      1. Size of agar plate always 150mm
      2. Depth of agar always thinly poured
      3. Media used always Mueller-Hinton (containing no PABARemember, sulfa drugs can be tested)
      4. Number of organisms spread on the plate is standardized (because the number of organisms placed on an agar surface is inversely proportional to the size of the zone of inhibition, due to the lag time between dropping the antibiotic disk on the plate and the drug diffusing into the agar)
      5. Size of antibiotic disks always 6mm
      6. Concentrations of antibiotic on the disks is standardized
      7. Incubation temperature in always 37°C

 

  1. Section 27.4: Mechanisms of Action
    1. Bacterial targets of antibiotics include—cell wall, cell membrane, DNA synthesis, RNA synthesis, protein synthesis, metabolism
    2. Cell wall antibiotics—obvious target peptidoglycan since eukaryotic cells lack
      1. Peptidoglycan structure and assembly
        1. Structure: made by linking sugar molecules N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) with a transglycosylase enzyme; NAM molecule contains a short sidechain of amino acids (made by ribosome); amino acid chains cross-linked together using transpeptidase enzyme; multiple units create cell-wall structure

 

  1. Assembly: uridine diphosphate (UDP)-NAM is made in cytoplasm, amino acids are added sequentially (five total: called NAM-pentapeptide); NAM-pentapeptide transferred to membrane bound bactoprenol molecule allowing NAG to be added again using the UDP intermediate; bactoprenol carrying NAM-NAG moves to other side of plasma membrane; transpeptidases and transglycosylases (called penicillin-binding proteins, PBPs) bind D-Ala-D-Ala, transglycosylase binds it to next sugar, transpeptidases bind to neighboring amino acid chain (L-lys to D-Ala, with terminal D-Ala removed in the process); last, a phosphate group is removed from the bactoprenol, which causes it to flip back into the intracellular side of the plasma membrane and pick up another subunit
  1. Penicillin and other beta-lactams—target penicillin-binding proteins
    1. Formed by a cysteine and valine combining to form beta-lactam ring structure; different R groups can be added to basic structure to change antibiotic spectrum and/or stability
    2. Structure chemically resembles D-Ala-D-Ala, molecular mimicry allows drug to bind transpeptidases and transglycosylases (thus, the name penicillin-binding proteins); halting peptidoglycan process
    3. Bacterial cell bursts due to lack of cell wall restraint, therefore bactericidal
    4. Most effective against Gram-positive organisms because drug has difficulty passing through Gram-negative outer cell wall
    5. Ampicillin—a modified penicillin penetrates Gram-negative more easily and more effective against Gram-negatives (broader spectrum)
  • Penicillin resistance: two ways
    1. Inheritance of a gene encoding one of the beta-lactamase enzymes, cleaves bet-lactam ring (secreted extracellularly, surrounding media for Gram-positives, periplasmic space for Gram-negatives); can still be susceptible to modified penicillins (g., cephalosporins and methicillin)
    2. Inheritance of mutation in penicillin-binding proteins, no longer can physically bind to penicillin (methicillin-resistant organisms work this way, g., MRSA—methicillin-resistant Staphylococcus aureas, vancomycin one of the few remaining drugs left for MRSA)
  1. Cephalosporins—another beta-lactam drug discovered in nature, modified in the lab to fight penicillin resistant organisms
    1. Each lab modification has made the drug increasingly complex and effective; each modification named a new “generation”—currently four generations of cephalosporins
    2. Resistance has developed by way of evolution of new beta-lactamases that can reach buried beta-lactam rings within these molecules
    3. Cross-sensitivity with all beta-lactam drugs is possible since all share beta-lactam ring
  2. Bactracin—produced by Bacillus subtilis and Bacillus licheniformis
    1. Mechanism of action: binds bactoprenol molecule inhibiting transport of the monomeric peptidoglycan units but inhibited dephosphorylation of the carrier
    2. Resistance: rapid recycling of carrier or drug export system
  3. Cycloserine—produced by Streptomyces garyphalus, treat tuberculosis
    1. Mechanism of action: inhibits the two enzymes that make the D-Ala-D-Ala dipeptide, amino acid side chain cannot be made

 

  • Vancomycin—produced by Amycolatopsis orientalis
    1. Mechanism of action: binds the D-Ala-D-Ala terminal amino acid preventing action of the transpeptidases and transglycosylases
    2. Drug of last resort, to prevent development of resistance since so good at treating other beta-lactam resistance bacteria
    3. Resistance: van genes form D-Ala-D-lactate (instead of D-Ala-D-Ala), vancomycin no longer has a binding site
  • All drugs that effect the cell wall do so only in growing bacteria, static or stationary phase bacteria will not be affected
  1. Bacterial membrane inhibitors—few compounds which can poke holes into the bacterial cell membrane, destroying cellular integrity
    1. Gramicidin—produced by Bacillus brevis, cyclic peptide composed of 15 alternating D- and L-amino acids, inserts into membrane forming cationic channel
    2. Polymyxin—produced by Bacillus polymyxa, cyclic peptide ring positively charged binds to lipid A (outer membrane) and inner membrane, detergentlike destruction
  • Can only be used topically because drugs can interact with eukaryotic cell membranes
  1. DNA synthesis inhibitors—several classes of drugs including sulfa, quinolones, and metronidazole affect bacterial DNA synthesis
    1. Sulfa drugs—antimetabolite drug, interferes with the synthesis of metabolic intermediates, ultimately interfering with synthesis of nucleic acids
      1. Prevent synthesis of tetrahydrofolic acid (THF), a necessary cofactor for nucleic acid precursors
      2. Higher mammals use dietary folic acid for THF production, bacteria rely on PABA precursor for THF production, sulfa drug is a PABA structural analog selectively blocking the bacterial synthesis, not mammalian synthesis
    2. Quinolones—target microbial DNA gyrase and topoisomerase IV, enzymes distinct to bacteria therefore drug is selective
      1. Nalidixic acid—an example of a quinolone drug, discovered in 1963 as a by-product of chloroquine production; targets DNA gyrase; very narrow spectrum covering only a few Gram-negative organisms
      2. Addition of fluorine and amine groups to nalidixic acid have increased its antimicrobial spectrum and bloodstream half-life resulting in class of drugs called quinolones and fluoroquinolones
  • Metronidazole—prodrug found in aerophilic and anaerobic bacteria such as Bacteroides; activated after the drug receives an electron (is reduced) from microbial cofactors flavodoxin and ferredoxin; once activated randomly nicks DNA
    1. Effective against anaerobic bacteria and some protozoa (g., Giardia, Trichomonas, and Entamoeba); not effective against aerobic bacteria because ferredoxin preferentially reduces oxygen rather than the drug
  1. RNA synthesis inhibitors—inhibit transcription processes
    1. Actinomycin D—bactericidal, active against growing bacteria; tricyclic ring binds DNA nonselectively; not prescribed for treatment
    2. Rifampin—bactericidal, active against growing bacteria; binds bacterial RNA polymerase (RNAP) subunit selectively; transcription occurs but rifampin obstructs exit tunnel for new RNA; often prescribed for tuberculosis and meningococcal meningitis; turns patients bodily secretions orange while on the drug (harmless)

 

  • Pyronins—new class of drugs produced by Myxococcus fulvis, prevents RNAP from ever starting polymerization; bind to hinge region of RNA polymerase where DNA strands are separated (melt), no separation, no start of transcription; useful for rifampin-resistant strains; extremely low possibility of pyronin-resistance because mutation in this part of the bacterial system would be potentially deadly to the bacteria
  1. Protein synthesis inhibitors—based on the differences in ribosome structure between prokaryotes and eukaryotes, especially rRNA structure/function differences; most are bacteriostatic; subdivided into groups based on their structures and part of translation machinery begin targeted
    1. Protein synthesis inhibitors that affect 30S ribosomal subunit
      1. Aminoglycosides: bactericidal; contain a cyclohexane ring and amino sugars; bind 16S ribosomal subunit and cause translational misreading of mRNA; examples: streptomycin and gentamycin; major, but uncommon, side effect is hearing damage.
      2. Tetracyclines: bacteriostatic; four fused cyclic rings; bind and distort the ribosomal A site that accepts incoming charged tRNA molecules; example doxycycline used to treat Lyme disease
        (Borrelia burgdorferi) and acne (Propionibacterium acnes); side effect: interfere with bone development in fetus/ young child; discolor teeth, not recommended for pregnant women
    2. Protein synthesis inhibitors that affect 50S ribosomal subunit: five classes of drugs
      1. Macrolides: bacteriostatic; 14- to 16-member lactone ring; inhibit translocation of the growing peptide; examples: erythromycin and azithromycin; used in penicillin-sensitive patients
      2. Lincoamides: similar to macrolides in function, different structure; example clindamycin
      3. Chloroamphicol: bacteriostatic; inhibits peptidyltransferase activity; aplastic anemia serious side effect limits clinical usage
      4. Oxazolidinones: recently discovered, synthetic antibiotics; effective against many antibiotic resistant microbes; example linezolid, binds 23S rRNA in the 50S subunit, preventing formation of the 70S initiation complex; limited resistance due to multiple operons encoding 23S rRNA; primarily used against Gram-positive bacteria; Gram-negative intrinsically resistant due to MDR pumps and decreased permeability of outer membrane
      5. Streptogramins: produced by some Streptomyces species; two groups A and B; group A have large nonpeptide ring, group B are cyclic peptides; both inhibit bacterial protein synthesis by binding to the peptidyltransferase site; group A distorts the ribosome to prevent tRNA binding to ribosome A site; group B narrow exit site and prevent exit; natural streptogramins are a mixture of A and B—more potent together than alone due to synergistic effect (e., binding of A increases affinity for B binding); Synercid is the marketed name for commercial drug; resistance can develop through ribosomal modification of 23S rRNA, production of inactivating enzymes or efflux pumps

 

 

  1. Section 27.5: Antibiotic Biosynthesis (Antibiotics considered secondary metabolites because they often have no apparent use in the producing organism; may help microbes compete with one another in nature; may be useful in mutalistic relationships [e.g., microbe protects organism it colonizes from other pathogens; leaf-cutter ants and Streptomyces]; growth inhibition may not have been original purpose, probably used in cell–cell signaling)
    1. Penicillin and cephalosporin biosynthesis—pcbAB, pcbC, and penDE genes encode ACV synthetase, IPN synthetase, and IPN acyltransferase; CefD required to make penicillin N, then CefE synthetase required to make first cephalosporin structure
    2. Eyrthromycin and other polyketide antibiotics synthesized using a strategy similar to fatty acid synthesis; malonyl-ACP units containing different R groups are successively condensed by polyketide synthetase and terminated by thioesterase
    3. Bacitracin and gramicidins not synthesized using ribosomes (no mRNA)
    4. Why are the microbes that produce antibiotics not susceptible to their own metabolites?
      1. Penicillin—fungus does not have peptidoglycan; no target in organism that makes the drug
      2. Streptomycin or chloramphenicol—producing organism could be susceptible but avoids killing by two ways: (1) synthesizes inactive precursor secreted from the cell before activation; (2) producing organism has an enzyme to deactivate any of the antibiotic that leaks back in
  • Other organisms employ methylation of rRNA sites to protect themselves

 

  1. Section 27.6: The Challenges of Antibiotic Resistance: Increases in Drug-Resistant Bacteria Happening Throughout the World
    1. Examples—penicillin-resistance Streptococcus pneumoniae; Acinetobacter bauminii, nosocomial infection with increasing multidrug resistance
    2. Four basic forms of resistance
      1. Modify target so antibiotic cannot bind: mutations in penicillin-binding proteins and ribosomal proteins seen; occur spontaneously, not typically transferred between organisms
      2. Destroy antibiotic before entering the cell: beta-lactamases/penicillinases destroy penicillins by cleaving ring structure
  • Add modifying groups that inactivate the antibiotic: three classes of enzymes can inactivate aminoglycoside antibiotics
  1. Pump the antibiotic out using specific or nonspecific transport proteins: pumps drug out faster than drug can get in
    1. Some single-component pumps in cytoplasmic membrane of Gram-positives and Gram-negatives (g., NorA in Staphylococcus aureus, PmrA in Streptococcus pneumoniae, TetA/B in Gram-negatives)
    2. Multidrug resistance efflux pumps (MDR)—particularly concerning since they can pump out many different types of drugs (nonspecifically); similar to ABC transporters; include three proteins: (1) inner membrane protein pump (fueled by proton motive force), (2) outer membrane channel connected to protein pump, and (3) accessory protein linking other two proteins; example of MDR ArcB transporter system
    3. Contribute significantly to bacterial resistance because of the broad range of substrate bound and expression in important pathogens; example Mycobacterium tuberculosis MDR increasing worldwide

 

  1. How drug resistance develops—through evolution, gene duplication, and mutational reshaping due to genomic plasticity; however, many species inherit the resistance through horizontal gene transfer methods (g., conjugation)
    1. Example: Enterococcus faecalis, natural inhabitant of mammalian GI tract; naturally resistant to numerous antibiotics; vancomycin one of last drugs of treatment for infection; increasing vancomycin-resistance seen in recent years; genetic sequencing has revealed that a quarter of the genome consists of mobile or exogenously acquired DNA (7 prophages, 38 insertion sequences, transposons, and integrated plasmid sequences); one of these mobile elements encodes for the resistance
    2. Integrons—gene expression elements that account for rapid transmission of drug resistance due to their mobility and ability to collect resistance gene cassettes (e.g., MDR seen in Salmonella enterica)
  • Resistance comes at a price; resistant bacteria usually not as vital as wild type (unless in the presence of the antibiotic)
  1. Resistance has become a problem due to the overuse and nondiscriminant use of antibiotics; more antibiotic used, the greater the chance of resistance; antibiotics should be administered prudently when possible (excluding life-threatening situations or certain conditions that justify bacterial infection [g., immunodeficiency]); resistance also increasing due to agricultural practices that add antibiotics to animal feed
  2. Fighting resistance—many strategies being used or looked into
    1. Dummy target compounds: example—clavulanic acid is a beta-lactam with no antimicrobial properties, if given in combination with a beta-lactam drug it will compete for binding with any secreted beta-lactamase, binding of clavulanic acid to beta-lactamase is slow to release allowing the beta-lactam drug to enter the cell
    2. Alter antibiotic structure in a way that sterically hinders the access to the modifying enzymes (e.g., alternation of gentamycin to amikacin)
  • Linking antibiotics forming hybrid antibiotic with dual action; harder to develop resistance to two modes of action in comparison with one (e.g., rate of spontaneous resistance to one antibiotic 1 out of 107 cells, rate of spontaneous resistance to one antibiotic 1 out of 1014 cells); MDR pumps and MDR gene cassettes will trump this strategy
  1. Antibiotic tolerance—unsolved microbiology problem are persister cells (cells that neither grow or die in the presence of an antibiotic, not antibiotic mutants but seem dormant); persisters found in any biofilm or population in late log phase exposed to antibiotics; these cells may explain antibiotic treatment failure and even latent bacterial infections (g., typhus or TB); since dormant antibiotics have little effect and these cells can regrow the bacterial population once the antibiotic is removed

 

  • Section 27.7: The Future of Drug Discovery
    1. Classical approach consists of collecting microbes, plants, animals, and screening for antimicrobial properties; advent of genetic sequencing has added another powerful tool to search for novel bacterial drug targets or validate theoretical targets;
    2. Modern drug discovery approach
      1. Identify new targets (such as unique essential enzymes) based on genomics
      2. Find or design compounds to inhibit in vitro and show antibacterial activity
  • Show target within the bacterial cell is same as in vitro target
  1. Optimize MICs against susceptible species by altering compound structure
  2. Examine compound’s spectrum of activity and rate of resistance
  3. Determine compound’s toxicity to animals and humans and its pharmacological properties (e.g., therapeutic levels, side effects, etc.)
  1. Gene functions that are targets of new drug development—products of the second and third categories (below) that are novel and essential constitute potential new targets
    1. Genes that control in vitro growth in lab media (in vitro expressed genes)
    2. Genes that control in vivo growth in humans (in vivo expressed genes)
  • Genes that control both in vitro and in vivo growth (housekeeping genes)
  1. Example—Streptococcus pneumoniae used to be sensitive to penicillin, now a growing number of strains are penicillin-resistant
    1. New targets identified through genomic scanning of sequence motifs of commonly found cell surface-exposed or virulence-related proteins of other bacteria; one domain identified choline-binding domain (CBD)
      1. CBD—repeats of 2–10 amino acids
      2. CbpA—a pneumococcal adhesin protein with an important role in nasopharyngeal colonization; using CbpA CBD researcher searched the genome and found six other genes encoding CBD-containing proteins (called CbpD, E, F, G, I, J)
      3. Mutant constructs of each of the newly discovered genes (CbpD, E, F, G, I, J) were done and it was found that CbpG defects effected nasopharyngeal binding and colonization
      4. CbpG may be a good target for new drug therapy due to importance in virulence and proteaselike structure (since many chemical protease inhibitors already exist)
    2. Some drug design using a combination of genomic and proteomic approaches, developing techniques to fluorescently tag active proteins with a given protein family, design of tags that bind to the active site of a protein can be use in screening potential antibiotics (less fluorescence if antibiotic binds to the active site); antibiotic options can be made using combinatorial chemistry and screened for inhibitory activity robotically
  • Screening natural products also still done, Merck scientists recently screened 250,000 natural product extracts for an ability to inhibit bacterial fatty acid biosynthesis (a good target due to the difference in pathways between prokaryotes and eukaryotes); found FabF protein an essential component of fatty acid synthesis that is conserved among key pathogens
    1. Strains of Staphylococcus aureas engineered with antisense RBA to fabF mRNA, prevent translation, decreased FabF protein, screened with inhibitors to FabF (fewer drug molecules needed in each screening since less FabF present creating larger zones on inhibition)
    2. Resulted in discovery of novel antibiotic platensimycin, made by Streptomyces platensis, isolated from South African soil
    3. Platensimycin binds FabF, exhibits bacteriostatic, broad-spectrum activity (both Gram-negative and Gram-positive); third novel antibiotic in four decades; novel chemical structure and novel target
  1. Other intriguing possibilities—nanotubes to poke holes in bacterial membranes; photosensitive chemicals that generate reactive oxygen species when exposed to visible light; “corking” the type II secretion apparatus; interfering with quorum-sensing mechanisms
    1. Quorum-sensing special topic: Pseudomonas aeruginosa biofilms—biofilms hard to destroy by antibiotics and immune mechanisms; cell–cell signaling (quorum sensing) very important to biofilm development so possible jamming of this signal may be of benefit; research aimed at destroying acyl homoserine lactones (AHL, signaling molecules) by different means (e.g., natural enzymes [paraoxonases], catalytic antibodies, etc.)
      1. One lab (Sperandio lab) looked at QseCB system in enterohemorrhagic coli (EHECs), Salmonella, Francisella, and other pathogens; this system senses a bacterial signal (autoinducer 3) and host adrenergic molecules to activate key virulence genes
      2. Lab screened 150,000 randomly synthesized small organic molecules that would block quorum sensing in the QseCB system
      3. One molecule LED209 selected (due to minimal bacterial and human cell line toxicity, potency, and potential for chemical modification), when tested reduced virulence in EHEC and Francisella in mice
    2. Quorum sensing approach promising but still very new; must be approached cautiously due to lack of knowledge, host and microbiota quorum sensing regulation, and not knowing consequences to human tissues

 

  • Section 27.8: Antiviral Agents (Fewer than antibiotics due to the fact that applying the principle of selective toxicity is much harder to achieve for viruses than for bacteria since viruses parasitize host cell functions)
    1. Anitviral agents that prevent virus uncoating or release—membrane-coated viruses are vulnerable during entrance and exit of a host cell
      1. Example: influenza virus—severe form reported in United States in 2003; higher-then-normal deaths in children and young adults; did not become an epidemic due to immunization (creating herd immunity) and due to antiviral agents
      2. Influenza envelope contains viral spike proteins of neuraminidase (NA) and hemagglutinin (HA); HA binds to host cell glycoproteins triggering receptor-mediated endocytosis; pH drop allows receptor change for HA to bind to endocytic compartment causing viral envelope fusion with endocytic membrane and virion release into cytoplasm
  • Two selective targets discovered to stop influenza
    1. Acidification of endocytic compartment is facilitated by viral-encoded M2 envelope protein—can be blocked by amantadine, a specific inhibitor to influenza M2 protein (effective against influenza A and H1N1); amantadine-resistance developing due to widespread use by Asian poultry farmers
    2. Neuraminidase inhibitors—NA needed for correct viral particle release, NA inhibitors cause NA to aggregate on surface decreasing number of viral particles released
    3. When both amantadine and neuraminidase inhibitors are used within 48 hours of infection, influenza duration can be reduced by one day (of benefit to elderly and children, minimizes lung damage and secondary bacterial infections)
  1. Antiviral DNA synthesis inhibitors—inhibit viral DNA synthesis;
    1. Chemical analogs of normal DNA nucleosides (AGCT), addition of phosphate by viral enzymes, and attachment to growing viral DNA strand stop further addition of nucleotides to strand (chain-terminating analogs)
    2. Selectively toxic because viral polymerases have a higher affinity to the chain terminating analogs than to the normal DNA nucleotides
  • Work only in DNA viruses or retroviruses (not RNA viruses)

 

  1. Nucleoside and nonnucleoside reverse transcriptase inhibitors—works on retroviruses because they contain reverse transcriptase (g., HIV); reverse transcriptase turns viral RNA into viral DNA for integration into the host cell nucleus
    1. Zidovudine (ZDV or AZT)—nucleoside analog that fools reverse transcriptase to incorporate it into the growing chain causing chain termination reaction
    2. Delavirdine—a non-nucleoside reverse transcriptase inhibitor binds directly to reverse transcriptase and allosterically inactivates enzyme
  • HIV therapy usually consists of combination to reduce resistance
  1. Protease inhibitors—within the host cell HIV proteolytic cleavage of a long polypeptide chain is necessary to make functional HIV viral proteins
    1. Gag and pol genes open reading frames are offset by one base creating a mRNA of two polyproteins called Gag and Gag-Pol; proteolytic cleavage allows these polyproteins to become capsid components (p. 17, p. 24, p. 15,
      p. 7) and enzyme proteins (reverse transcriptase and integrase)
    2. Protease inhibitors (Viracept and Lopinavir) block HIV protease, halting HIV maturation within a host cell, stalling disease
  • Protease inhibitor therapy recommended for patients with AIDS symptoms and asymptomatic patients with viral loads above 30,000 copies per milliliter

 

  1. Section 27.9: Antifungal Agents (Fungal infections harder to treat than bacterial infections since fungal physiology more similar to humans and fungi have efficient drug detoxification systems that can modify and detoxify many antibiotics; to have a fungistatic effect, repeat applications are necessary to keep levels of unmodified drug above MIC levels)
    1. Difference in treatment dependent on superficial or systemic mycoses
      1. Imidazole-containing drugs (clotrimazole, miconazole) used for superficial mycoses (skin, hair, nails, Candida infections of mucus membranes)—inhibit sterol synthesis
      2. Lamisil—inhibits ergosterol synthesis in fungi but not human cells; popular antifungal
  • Griseofulvin, an antifungal agent produced by the fungi Penicillium, used for chronic dermatophytic infections, disrupts mitotic spindle formation and derails cell division; does not kill the fungus but stops its growth, allowing for hair, skin, or nails to grow and shed infection
  1. Nystatin—used in vaginal Candida infections, synthesized by Streptomyces, forms membrane pores
  2. Amphotericin B—produced by Streptomyces, used in systemic mycoses; binds to sterols in fungal membrane and destroys membrane integrity; high affinity for ergosterol (found in fungal, but not human cell membranes), requires long-term treatment to prevent relapse
  3. Fluconazole—used in systemic mycoses; inhibits synthesis of ergosterol, requires long-term treatment to prevent relapse

Reviews

There are no reviews yet.

Be the first to review “Microbiology An Evolving Science 2nd Edition Slonczewski Foster Test Bank”

Your email address will not be published. Required fields are marked *