Therapeutic Antimicrobials III Flashcards
1
Q
list the 3 mechanisms for the acquisition of a resistance plasmid or transposon
A
- transformation
- DNA binding proteins
- conjugation
- plasmid
- transduction
- bacteriophage
2
Q
describe the process of transformation
A
- 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
3
Q
describe the process of conjugation
A
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)
4
Q
describe the 2 types of transduction
A
5
Q
describe generalized transduction
A
- 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
6
Q
describe specialized transduction
A
- 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
7
Q
describe the process of transposition
A
- types
- simple transposon: insertion sequences (IS)
- complex transposons: 2 x IS plus other genes
- can move around within the cell:
- chromosome -> plasmid
- chromosome -> chromosome
- = non-homologous recombination: site-specific recombinases
8
Q
summarize the mechanisms of gene transfer between bacteria
A
9
Q
name the 4 classes of antifungals that target three fungal synthesis pathways
A
10
Q
describe fluoropyrimidine analogs
A
- 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
11
Q
describe the polyenes
A
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
12
Q
describe the azols
A
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
13
Q
describe the synthesis of ergosterols and where drugs inhibit in the pathway
A
14
Q
describe the function of echinocandins
A
- 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
15
Q
summarize fungal resistance to antifungals
A
