Antibiotic Sensitivity and Resistance Lecture Notes

Flashcards covering antibiotic mechanisms, human toxicity, and bacterial resistance strategies based on Handout 6.

What is the specific target and mechanism of action for Penicillin?

It targets cell wall synthesis by binding and inactivating Penicillin-Binding Proteins (PBPs) like transpeptidase enzymes, which inhibits the transpeptidation reaction and blocks cross-linking of the peptidoglycan cell wall.

Why is Cefoxitin resistant to being broken down by $\beta$-lactamases?

Cefoxitin has a special chemical structure called a "methoxy group" that acts like a shield, preventing bacteria from degrading or inactivating the drug using defensive enzymes.

What is the mechanism of action for Streptomycin?

It binds to the $16S\,rRNA$ of the $30S$ ribosomal subunit, causing misreading of mRNA and premature cessation of protein synthesis.

Why is Gentamicin ineffective against strict anaerobes?

It requires oxygen-dependent active transport to enter the bacterial cell.

What is the effect of Erythromycin on protein synthesis?

It binds to the $50S$ ribosomal subunit and prevents the synthesis of polypeptide chains by inhibiting translation elongation, resulting in bacteriostatic effects.

Which enzyme does Chloramphenicol inhibit, and on which ribosomal subunit does it act?

It inhibits peptidyl transferase on the $50S$ ribosomal subunit, blocking the formation of peptide bonds.

How do Tetracyclines like Doxycycline inhibit protein synthesis?

They bind to the $30S$ ribosomal subunit and prevent aminoacyl-tRNA from binding to the A-site.

What is the target and action of Rifampicin?

It binds to the subunit of DNA-dependent RNA polymerase, inhibiting transcription (RNA synthesis).

Which enzymes are targeted by Nalidixic acid?

DNA gyrase (topoisomerase II) and topoisomerase IV.

Why do protein synthesis inhibitors often exhibit toxicity in humans?

Bacterial $70S$ ribosomes share structural similarities with human mitochondrial ribosomes, leading to off-target disruption of mitochondrial protein synthesis and energy failure.

What is the specific human toxicity associated with Chloramphenicol?

Bone Marrow Suppression (Aplastic Anemia).

What are the two key toxicities associated with Aminoglycosides like Gentamicin and Streptomycin?

Nephrotoxicity (Kidney) and Ototoxicity (Hearing/Balance).

How do bacteria achieve resistance to glycopeptides like vancomycin?

By modifying the peptidoglycan precursor (Lipid II) from $D\text{-Ala-}D\text{-Ala}$ to $D\text{-Ala-}D\text{-Lac}$ or $D\text{-Ala-}D\text{-Ser}$, which reduces the antibiotic's affinity.

What modification does Staphylococcus aureus use to become resistant to lysozyme?

$O\text{-acetylation}$ (via OatA), where acetyl groups are added to the $O\text{-}$ or $N\text{-acetylmuramic acid}$ ($\text{MurNAc}$) of the peptidoglycan layer.

Why are Mycobacteria naturally resistant to many antibiotics?

Their high lipid content (mycolic acids) provides a hydrophobic barrier that restricts the entry of hydrophilic antibiotics.

What three components make up the extracellular polymeric substance (EPS) matrix of biofilms?

Polysaccharides, DNA, and proteins.

What are the four primary mechanisms of bacterial resistance?

1. Impermeable barrier; 2. Efflux pumps; 3. Resistance mutation (target modification); 4. Drug inactivation (enzymatic degradation).

How do $\beta\text{-lactamases}$ cause drug inactivation?

They hydrolyze (cleave) the critical $\beta\text{-lactam}$ ring structure found in penicillins and cephalosporins.

Name the three main classes of Aminoglycoside-Modifying Enzymes (AMEs).

$N\text{-acetyltransferases}$ (AAC), $O\text{-phosphotransferases}$ (APH), and $O\text{-adenyltransferases}$ (ANT) or Nucleotidyltransferases.

What is the difference between 'Steric Hindrance' and 'Charge Disruption' in the context of AME resistance?

Steric Hindrance involves adding bulky groups that physically block the antibiotic from the ribosome; Charge Disruption involves adding charged groups (like phosphates) that alter the electrostatic dynamics and repel the drug from the binding pocket.

Which mechanism of horizontal gene transfer involves the use of plasmids and transposons?

Mobile genetic elements (MGEs).