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Flashcards in Therapeutic Antimicrobials III Deck (16)
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list the 3 mechanisms for the acquisition of a resistance plasmid or transposon

  • transformation
    • DNA binding proteins
  • conjugation
    • plasmid
  • transduction
    • bacteriophage


describe the process of transformation

  • the uptake of DNA, released by bacterial cell lysis, from outside the bacterial cell
  • usually occurs between related bacterial species
  • facilitated by bacterial DNA binding proteins located on bacterial cell membrane
  • requires calcium ion (Ca2+)
  • relatively low frequency in nature; but high bacterial #s make it an important route for gene transfer


describe the process of conjugation

only in G-ve bacteria

  • F (fertility) factor plasmid encodes for conjugation pilus
  • pilus brings F+ (donor) and F- (recipient) bacteria into contact
  • outer membrane proteins maintain contact
  • F plasmid nicked in donor; one strand transferred to recipient
  • synthesis of complementary strand and recirculation of plasmid in both
  • completion of transfer and cells separate (now 2 F+)


  • multiple drug resistance is usually plasmid encoded
  • in G+ve bacteria: no sex pilus (use adhesins for aggregation with recipient cells)


describe the 2 types of transduction


describe generalized transduction

  • chromosome of cell is broken up as a defense mechanism but replication of the bacteriophage continues
  • when bacteriophage is being assembled, a fragment of bacterial chromosome is packaged instead of phage DNA (generalized transduction)
  • new bacteriophage are released and infect a new cell, transferring the bacterial chromosome fragment 


describe specialized transduction

  • in some cases, phage integrates into the chromosome at a specific location "prophage"
    • when phage excises, it takes parts of neighboring bacterial chromosome from region of integration along with it


describe the process of transposition

  • types
    1. simple transposon: insertion sequences (IS)
    2. complex transposons: 2 x IS plus other genes
  • can move around within the cell:
    • chromosome -> plasmid
    • chromosome -> chromosome
  • = non-homologous recombination: site-specific recombinases


summarize the mechanisms of gene transfer between bacteria


name the 4 classes of antifungals that target three fungal synthesis pathways


describe fluoropyrimidine analogs

  • flucytosine 
  • entry is via fungal cytosine permease; then intracellular deamination by fungal cytosine deaminase (basis of the selective toxicity) converts to 5-fluorouracil 
    • can't give 5-FU directly to humans since it is toxic (chemotherapeutic drug)
  • inhibits synthesis of DNA, RNA and proteins


describe the polyenes

amphotericin B, Nystatin

  • extremely lipophilic: directly bind to ergosterol in fungal cell membrane
    • contrast with azoles interfere with synthesis of ergosterol
  • disrupts osmotic integrity of membrane --> ion leakage and membrane destabilization
  • fungicidal: activity against most yeasts and filamentous fungi


describe the azols

most widely used antifungals in clinical practice

  • imidazoles (2 nitrogens)
  • triazoles (3 nitrogens)
    • newer
    • reduced toxicity; higher efficacy
    • e.g. Fluconazole, Voriconazole
  • 250 fold higher affinity for enzymes involved in synthesis of fungal sterols compared to mammalian cholesterol
  • effect on growth: fungistatic or fungicidal (depends on species and specific compound)
  • some have anti-parisitic effects


describe the synthesis of ergosterols and where drugs inhibit in the pathway


describe the function of echinocandins

  • blocks B-(1,3)-D-glucan synthase
  • involved in cell wall formation [B(1-3)-glucans + chitin]
  • Nikkomycin Z - currently under investigation in terms of therapeutic potential
    • prevents synthesis of chitin


summarize fungal resistance to antifungals


describe the function of neuraminidase inhibitors

  • normal role of viral neuraminidase (cleaves sialic acid from glycoproteins):
    • entry
      • prevents virus being trapped in mucus
    • exit
      • prevents binding of HA on budding virus to cell surface sialic acids
  • block neuraminidase --> formation of viral aggregates at cell surface
    • i.e. release of newly budded virus is blocked