Antibiotics and Anti-Fungals Flashcards by Wasim Silmi

antibiotic intracellular process targets? (4)

nucleic acid synthesis, DNA replication, RNA synthesis and protein synthesis

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antibiotic cell membrane targets? (3)

peptidoglycan synthesis
peptidoglycan incorporation
membrane stability

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antibiotic resistance mechanisms? (5)

destruction enzymes
additional target
hyper-production
changes to target
alterations in permeation

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2 types of anti-fungals?

azoles and polyenes

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3 types of bacteria? example of each

gram +ve staph. aureus, gram -ve e. coli and mycolic mycobacterium tuberculosis

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Describe the 4 stages for DNA synthesis in bacteria

NUCLEIC ACID SYNTHESIS:
paraaminobenzoate (PABA) -> [DHOp synthase] -> dihydropteroate (DHOp) -> dihydrofolate (DHF) -> [DHF reductase] -> tetrahydrofolate (THF)
- THF is Important in DNA synthesis
DNA REPLICATION:
DNA gyrase
- Topoisomerase unwinds bacteria DNA, releases tension and provides access for enzymes
RNA SYNTHESIS:
RNA polymerase
- Produces RNA from DNA template
- Differ from eukaryotic RNA polymerase
PROTEIN SYNTHESIS:
Ribosomes
- Produce protein from RNA templates
- Differ from eukaryotic ribosomes

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Describe the pathway for synthesis of tetrahydrofolate

paraaminobenzoate (PABA) -> [DHOp synthase] -> dihydropteroate (DHOp) -> dihydrofolate (DHF) -> [DHF reductase] -> tetrahydrofolate (THF)

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What is the use of tetrahydrofolate

important in DNA synthesis

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What inhibits DHOp synthase

sulphonamides

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what inhibits DHF reductase

Trimethoprim

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Target of sulphonamides

Inhibits DHOp synthase

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Target of Trimethoprim

inhibits DHF reductase

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drugs that target bacterial DNA synthesis pathway?

sulphonamides

Trimethoprim

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Target of Fluoroquinolones

inhibit DNA gyrase & topoisomerase IV

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Drug that targets DNA gyrase

Fluoroquinolones

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Drug that targets topoisomerase IV

Fluoroquinolones

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What enzymes are involved in unwinding DNA in bacterial DNA replication

DNA gyrase & topoisomerase IV

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Target of Aminoglycosides

bacterial Ribosomes

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Target of Chloramphenicol

bacterial Ribosomes

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Target of rifamycins

bacterial RNA polymerase

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Target of Macrolides

bacterial Ribosomes

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Target of Tetracyclines

bacterial Ribosomes

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Drug that targets bacterial Ribosomes

Macrolides
(Aminoglycosides
Chloramphenicol
Tetracyclines)

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Drug that targets bacterial RNA polymerase

rifamycins

Describe three stages of bacterial wall synthesis

1. PEPTIDOGLYCAN (PtG) SYNTHESIS: - A pentapeptide is created on N-acetyl muramic acid (NAM) - N-acetyl glucosamine (NAG) associates with NAM forming PtG 2. PtG TRANSPORTATION: - PtG is transported across the membrane by bactoprenol 3. PtG INCORPORATION: - PtG is incorporated into the cell wall when transpeptidase enzyme cross-links PtG pentapeptides

how do we inhibit PtG synthesis

- Glycopeptides (e.g. Vancomycin) bind to the pentapeptide preventing PtG synthesis

how do we inhibit PtG transportation

• Bacitracin inhibits bactoprenol regeneration preventing PtG transportation

how do we inhibit PtG incorporation

- b-lactams bind covalently to transpeptidase inhibiting PtG incorporation into cell wall - b-lactams include Carbapenems, cephalosporins and penicillins

how do we inhibit CELL WALL STABILITY

- Lipopeptide - (e.g. daptomycin) disrupt Gram +ve cell walls - Polymyxins - binds to LPS & disrupts Gram -ve cell membranes

What do Glycopeptides do

bind to the pentapeptide preventing PtG synthesis

What binds to the pentapeptide preventing PtG synthesis

Glycopeptides

What does Bacitracin do

inhibits bactoprenol regeneration preventing PtG transportation

What do b-lactams do

bind covalently to transpeptidase inhibiting PtG incorporation into cell wall

What does Lipopeptide do

disrupt Gram +ve cell walls

What do Polymyxins do

binds to LPS & disrupts Gram -ve cell membranes

Common example of a beta lactam?

Penicillin

what inhibits bactoprenol regeneration preventing PtG transportation

Bacitracin

what binds covalently to transpeptidase inhibiting PtG incorporation into cell wall

beta-lactam

what disrupts Gram +ve cell walls

lipopeptide

what binds to LPS & disrupts Gram -ve cell membranes

polymyxins

What 2 things come together to form PtG

- N-acetyl glucosamine (NAG) | on N-acetyl muramic acid (NAM)

what transports PtG across the bacterial membrane

bactoprenol

what enzyme incorporates PtG into the cell wall

transpeptidase

what does transpeptidase do

incorporates PtG into the cell wall by cross linking PtG pentapeptides

what does bactoprenol do

transports PtG across the bacterial membrane

4 causes of AB resistance?

1. Unnecessary prescription ~ 50% of antibiotic prescriptions not required 2. Livestock farming ~ 30% of UK antibiotic use in livestock farming 3. Lack of regulation OTC availability in Russia, China, India 4. Lack of development Very few antibiotics in recent years

Difference between gram +ve and gram -ve bacteria and mycolic?

Gram Positive Bacteria: - Prominent peptidoglycan cell wall Gram Negative Bacteria: - Outer membrane with lipopolysaccharide Mycolic Bacteria: - Outer mycolic acid layer

Give an example of AB resistance via Production of destruction enzymes

b-lactamases hydrolyse C-N bond of the b-lactam ring

Example of AB resistance via Additional target

E Coli produce different DHF reductase enzyme making them resistant to trimethoprim

Explain and give example of AB resistance via Alterations in target enzymes

Alteration to the enzyme targeted by the drug. Enzyme still effective but drug now ineffective S Aureus - Mutations in the ParC region of topoisomerase IV confers resistance to quinolones

give example of AB resistance via hyperproduction

Bacteria significantly increase levels of DHF reductase | Example E Coli produce additional DHF reductase enzymes making trimethoprim less effective

Explain AB resistance via Alterations in drug permeation

Reductions in aquaporins which are needed for the drug to get into the cell & increased efflux systems

What resistance do e coli show

E Coli produce different and additional DHF reductase enzymes making them resistant to trimethoprim

What resistance do S Aureus show

Mutations in the ParC region of topoisomerase IV confers resistance to quinolones

4 classifications of antifungals?

1. Superficial - Outermost layers of skin 2. Dermatophyte - Skin, hair or nails 3. Subcutaneous - Innermost skin layers 4. Systemic - Primarily respiratory tract

2 types of antifungals?

1. Azoles: Fluconazole | 2. Polyenes: Amphotericin

MOA azoles?

- Inhibit cytochrome P450-dependent enzymes involved in membrane ergosterol synthesis - Fluconazole (oral) candidiasis & systemic infections

MOA polyenes

- Interact with cell membrane ergosterolsforming membrane channels - Amphotericin (I-V) systemic infections