Antibacterial modes of action Flashcards
What is the difference between an antibacterial and an antibiotic?
Antibacterial refers to any chemical that specifically targets bacteria to kill or inhibit their growth.
Antibiotic originally referred to an antimicrobial agent produced by a microorganism, but now it commonly means a drug used to treat bacterial infections.
What does “bactericidal” mean, and how is it different from “bacteriostatic”?
Bactericidal drugs kill bacteria.
Bacteriostatic drugs slow down or stall bacterial growth without killing the bacteria directly.
What is selective toxicity, and why is it important in antibacterial therapy?
Selective toxicity means that the antibacterial agent selectively kills or inhibits the bacterial cells while causing minimal or no harm to the host (human cells). This property is crucial to avoid harmful side effects in the patient.
Name four major cellular targets of antibacterial drugs.
Cell wall
Protein synthesis
Nucleic acid synthesis
Cell membrane
What is the primary mode of action of beta-lactam antibiotics like penicillin?
Beta-lactams inhibit the cross-linking of peptide side chains in bacterial cell walls by binding to penicillin-binding proteins (PBPs), which prevents the formation of a stable peptidoglycan layer, leading to cell lysis.
How do glycopeptides, like vancomycin, inhibit bacterial cell wall synthesis?
Glycopeptides inhibit cell wall synthesis in two ways:
They bind to the last two amino acids (Ala-Ala) of the peptide side chain, preventing cross-linking.
They prevent the addition of peptidoglycan monomers to the growing chain by inhibiting the glycosylase enzyme.
Why are beta-lactams generally more effective against Gram-positive bacteria than Gram-negative bacteria?
Beta-lactams are more effective against Gram-positive bacteria because these bacteria have a mesh-like cell wall that beta-lactams can easily penetrate to reach the PBPs. Gram-negative bacteria have an additional outer membrane, and beta-lactams must pass through small porin channels, which limits their effectiveness.
What are autolysins, and how do they relate to the action of beta-lactam antibiotics?
Autolysins are enzymes produced by bacteria that break down their own cell walls. Beta-lactam antibiotics can stimulate the production of autolysins, leading to further degradation of the bacterial cell wall and contributing to cell lysis.
How do fluoroquinolones, such as ciprofloxacin, inhibit bacterial DNA synthesis?
Fluoroquinolones bind to and inhibit DNA gyrase and/or topoisomerase IV. These enzymes are essential for removing DNA supercoils and separating replicated DNA, which prevents DNA replication and leads to bacterial cell lysis.
Name two classes of antibiotics that target bacterial nucleic acid synthesis and give an example of each.
Fluoroquinolones - Example: Ciprofloxacin
Rifamycins - Example: Rifampicin
What is the difference between how tetracyclines and aminoglycosides inhibit protein synthesis?
Tetracyclines bind reversibly to the A-site on the 30S ribosomal subunit, blocking the binding of tRNA and inhibiting protein synthesis, making them bacteriostatic.
Aminoglycosides bind irreversibly to the same 30S subunit, preventing the formation of the initiation complex, causing misreading of mRNA, and increasing membrane permeability, making them bactericidal.
Why are glycopeptides like vancomycin ineffective against Gram-negative bacteria?
Glycopeptides are large molecules that cannot pass through the outer membrane of Gram-negative bacteria, preventing them from reaching their target, the peptidoglycan layer, and inhibiting cell wall synthesis.
What is the role of peptidoglycan in bacterial cell walls?
Peptidoglycan provides structural support to bacterial cell walls by creating a strong, mesh-like layer. It consists of glycan chains (alternating NAG and NAM) cross-linked by short peptide side chains, which give rigidity in both horizontal and vertical directions.
What is the significance of porin channels in Gram-negative bacteria?
Porin channels allow small, hydrophilic molecules, including some antibiotics, to pass through the outer membrane of Gram-negative bacteria. Antibiotics that cannot pass through these channels are less effective against Gram-negative bacteria.
How do sulphonamides and trimethoprim inhibit bacterial nucleic acid synthesis?
Sulphonamides and trimethoprim inhibit bacterial nucleic acid synthesis by acting as metabolic inhibitors, blocking enzymes involved in the synthesis of folate, a precursor for nucleotides, which are essential for DNA and RNA synthesis.
