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What is an opportunistic pathogen?

A pathogen that causes disease in a weakened host or when entering unusual locations.

Define nosocomial infection.

An infection acquired in a hospital.

What is zoonosis?

A disease that spreads from animals to humans.

Do bacteria have a nucleus?

No.

What differentiates Gram-positive from Gram-negative bacteria?

Gram-positive

What is the main difference in cell wall structure of mycobacteria?

Waxy, hydrophobic wall rich in mycolic acids; not Gram-stainable.

What are ideal characteristics of anti-infective drugs?

Selectivity, low host toxicity, broad specificity, and minimal resistance development.

Name three targets of antibacterial drugs.

Cell wall, ribosomes, DNA/RNA synthesis.

What mechanisms lead to antimicrobial resistance?

Increased efflux, decreased uptake, enzymatic destruction, target modification.

What are ESKAPE pathogens?

A group of resistant bacteria responsible for most hospital infections.

What is variolation?

Deliberate infection with live organism to build immunity.

Name a modern method of vaccination.

Injection with mRNA coding for antigens

What is the primary target of β-lactam antibiotics?

The transpeptidase enzyme (penicillin-binding protein) involved in peptidoglycan crosslinking.

Which enzyme catalyses the crosslinking of peptidoglycan in bacterial cell walls?

Transpeptidase.

Name the repeating disaccharide units in peptidoglycan.

N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM).

What is the structure of the pentapeptide in Gram-positive bacteria?

L-Ala–D-Glu–L-Lys–D-Ala–D-Ala.

What type of enzyme is also known as a penicillin-binding protein (PBP)?

Transpeptidase.

Describe the mechanism of action of penicillin on transpeptidase.

Penicillin covalently binds the active site serine of transpeptidase, blocking peptidoglycan crosslinking.

How does penicillin structurally mimic the D-Ala-D-Ala dipeptide?

It has similar bond lengths and spatial arrangement to D-Ala-D-Ala, fitting the active site of the enzyme.

What role does the catalytic serine play in the function of transpeptidase?

It attacks the peptide bond in D-Ala-D-Ala, allowing crosslinking.

Why does penicillin bind irreversibly to its target?

It forms a covalent acyl-enzyme complex with the catalytic serine.

Why are β-lactam antibiotics only effective against actively dividing bacteria?

Because they target cell wall synthesis, which only occurs during cell division.

What are β-lactamases, and how do they confer resistance?

Enzymes that hydrolyze the β-lactam ring, inactivating the antibiotic.

How do bulky R-groups on penicillins help resist β-lactamase activity?

They sterically hinder the enzyme’s access to the β-lactam ring.

What is clavulanic acid, and how is it used in therapy?

A β-lactamase inhibitor used in combination with β-lactam antibiotics.

Why is clavulanic acid not effective as a standalone antibiotic?

It has weak activity against PBPs but blocks β-lactamases.

Name two synthetic β-lactamase inhibitors besides clavulanic acid.

Sulbactam and tazobactam.

Compare the ring systems of penicillins and cephalosporins.

Penicillins have a thiazolidine ring; cephalosporins have a dihydrothiazine ring, which is less strained.

Why are cephalosporins more resistant to β-lactamase degradation?

Their ring structure is less reactive and more stable.

What structural features make carbapenems highly resistant to β-lactamases?

Trans-stereochemistry, lack of ring sulfur, and increased ring strain.

Name one advantage and one limitation of methicillin.

Advantage

What was the source organism for cephalosporin C?

Acremonium chrysogenum (isolated from Sardinian sewer water).

Explain why β-lactam antibiotics are selectively toxic to bacteria but not humans.

Humans lack peptidoglycan cell walls and transpeptidase enzymes.

How could a mutation in transpeptidase reduce β-lactam antibiotic effectiveness?

It could reduce binding affinity for β-lactams.

Why are β-lactams generally ineffective against dormant or slow-growing bacteria?

These bacteria are not actively synthesising cell walls.

Which class of β-lactam drugs would you choose to treat a multi-resistant Gram-negative infection, and why?

Carbapenems, due to their broad spectrum and resistance to β-lactamases.

Describe one mechanism by which bacteria could become resistant to β-lactamase inhibitors.

Mutation of β-lactamase to reduce inhibitor binding or expression of inhibitor-resistant enzymes.

What enzyme does moenomycin inhibit?

Transglycosylase.

Why is moenomycin not used in human medicine?

It has poor pharmacokinetics (PK).

Which step in peptidoglycan synthesis does moenomycin block?

The polymerization of Lipid II into glycan chains.

How does vancomycin inhibit bacterial cell wall synthesis?

It binds to the D-Ala-D-Ala tail of Lipid II, blocking enzyme access.

What part of the peptidoglycan precursor does vancomycin bind to?

The D-Ala-D-Ala terminus of the peptide chain.

What dual function does vancomycin block through binding D-Ala-D-Ala?

Both transglycosylase and transpeptidase activity.

What type of bacteria is vancomycin typically used to treat?

Resistant Gram-positive bacteria (e.g., MRSA, C. difficile).

Why is vancomycin usually administered intravenously?

It has poor oral absorption.

What structural change causes vancomycin resistance?

Replacement of D-Ala-D-Ala with D-Ala-D-Lactate.

Why does switching D-Ala-D-Ala to D-Ala-D-Lactate confer resistance?

The NH group is replaced by an O, reducing vancomycin binding affinity 1000-fold.

What is the mechanism of transglycosylation in peptidoglycan biosynthesis?

Nucleophilic attack by 4-OH of incoming Lipid II on C1 of the donor sugar in a β1,4 linkage.

Which residues in transglycosylase are critical for catalysis?

E114 and E171.

What is Lipid II, and why is it important in cell wall biosynthesis?

It is the membrane-bound peptidoglycan precursor that donates sugars and peptides to growing chains.

What is the role of the lipid carrier in peptidoglycan synthesis?

It transports NAG-NAM units across the membrane.

What is meant by “steric block” in vancomycin’s mechanism?

Vancomycin physically prevents enzymes from accessing their substrate.

What is the prodrug of sulfanilamide?

Prontosil.

What was sulfanilamide originally derived from?

An azo dye (Prontosil).

Which enzyme do sulfonamides inhibit?

Dihydropteroate synthetase.

What molecule do sulfonamides mimic to act as competitive inhibitors?

Para-aminobenzoic acid (PABA).

Why are sulfonamides bacteriostatic rather than bactericidal?

They inhibit growth by blocking nucleotide synthesis but don’t kill directly.

List the three key enzymes involved in tetrahydrofolate synthesis.

Dihydropteroate synthetase, dihydrofolate synthetase, dihydrofolate reductase.

Which enzyme does trimethoprim inhibit?

Dihydrofolate reductase (DHFR).

What is the combined effect of sulfonamide and trimethoprim?

Bactericidal action through sequential blockade of folate synthesis.

Why is the combination therapy considered bactericidal?

It blocks two steps in folate metabolism, halting DNA synthesis and killing the cell.

Why are sulfonamides and trimethoprim selectively toxic to bacteria?

Humans don’t use dihydropteroate synthetase and have a DHFR less sensitive to trimethoprim.

What is ergosterol and why is it important?

It is an essential component of fungal cell membranes, similar to cholesterol in humans.

What polymer is found in fungal cell walls?

Chitin and sometimes cellulose.

Which enzyme does terbinafine inhibit?

Squalene monooxygenase (squalene epoxidase).

What is the effect of terbinafine on fungal cells?

It blocks ergosterol synthesis, inhibiting cell membrane formation and slowing growth or causing death.

How does terbinafine achieve selectivity for fungi over humans?

It binds fungal squalene monooxygenase more effectively due to structural differences.

What is the key function of CYP51A1 in fungi?

It catalyzes the demethylation of lanosterol in ergosterol biosynthesis.

Which class of antifungal drugs inhibits CYP51A1?

Azole drugs.

What part of CYP51A1 do azole drugs bind to?

The iron atom in the heme group.

What was the first azole antifungal drug?

Ketoconazole.

Why does ketoconazole have poor selectivity?

Its binding pocket interactions can also occur in human P450 enzymes.

How do second- and third-generation azoles differ from ketoconazole?

They contain triazole rings for improved potency, selectivity, and pharmacokinetics.

Name two second- or third-generation azole drugs.

Fluconazole and voriconazole.

What is the common mechanism of action for azoles?

Inhibition of CYP51A1, blocking ergosterol synthesis and cell membrane formation.

What is the mechanism of Amphotericin B?

It binds to ergosterol and forms pores in the fungal membrane.

What is the result of pore formation by Amphotericin B?

Loss of ions and membrane integrity, leading to fungal cell death.

Name one reason Amphotericin B is effective but toxic.

It can also bind cholesterol in human membranes.

What are the three main antifungal drug classes discussed?

Allylamines (terbinafine), azoles (e.g., fluconazole), and polyenes (amphotericin B).

Which antifungal targets squalene monooxygenase?

Terbinafine.

Which antifungal targets lanosterol demethylase?

Azole drugs like ketoconazole.

Which antifungal forms membrane pores by binding ergosterol?

Amphotericin B.

Why is ergosterol a good drug target?

It is unique to fungi and essential for membrane integrity.

What is the target of some antibacterial drugs involved in protein synthesis?

The ribosome.

Why is inhibiting protein synthesis effective against bacteria?

Protein synthesis is essential for bacterial survival.

How do aminoglycosides inhibit protein synthesis?

Bind to 30S and 50S ribosomal subunits, causing mRNA miscoding, inhibiting translocation, and blocking ribosome recycling.

Are aminoglycosides bactericidal or bacteriostatic?

Bactericidal.

Which bacteria are aminoglycosides especially effective against?

Gram-negative bacteria including Pseudomonas aeruginosa.