Lecture 9. Mode of Action Flashcards
What are biofilms?
An assembly of microbial cells associated with a surface, and enclosed in an extracellular matrix made principally of polysaccharides
What are biofilm-associated organisms fundamentally different from?
Populations of suspended (planktonic) cells
What does the formation of biofilms allow bacteria to become?
Tolerant to antibiotics/antimicrobials, and generates resistance
What does slow diffusion lead to?
Tolerance
What do sublethal concentrations of antimicrobials in the biofilm lead to?
Selection of antimicrobial resistance (AMR)
What is the antibiotic resistance mechanism in Gram-negative bacteria?
Intrinsic - have a double-membrane structure that makes the cellular envelope relatively impermeable
What is the antibiotic resistance mechanism in Gram-positive bacteria?
Acquired - Alterations to envelope structure, such as porin loss reduce permeability to antibiotics leading to acquired antibiotic resistance
What are two examples of non-specific antibiotic resistance mechanisms?
Porins and efflux pumps
What do efflux pumps do?
Decrease the concentration of antibiotic within the cell
What antibiotics target cell wall synthesis?
Penicillins
Cephalosporins
Carbapenems
Monobactams
What antibiotics target nucleic acid synthesis?
Quinolones
What antibiotics target the 30S subunit in the ribosome?
Amicoglycosides
Tetracyclines
What antibiotics target the 50S subunit in the ribosome?
Macrolides
Chloramphenicol
What is a β-lactam antibiotic?
A member of a large group of broad-spectrum agents related to β-lactam
What do most β-lactam antibiotics target?
Penicillin-binding proteins
What are penicillin-binding proteins?
Penicillin-binding proteins (PBPs) are DD-transpeptidases that make cross-links (peptide bonds) between D-amino acid residues in sugar-lined pentapeptides in the bacterial cell walls
Essential for bacterial cell wall synthesis
How do β-lactam antibiotics work?
The reactive β-lactam ring binds the active site of the transpeptidase, permanently inactivating D-alanine the PBP: cell wall cross-linking ceases
What are the four ways resistance to β-lactam antibiotics can occur?
- Mutation of PBP, lowering the affinity for penicillins, etc
- Down-regulation of porins in Gram-negative bacteria
- Acquisition of β-lactamase- ESBL (extended spectrum β-lactamase)
- Up-regulation of efflux pumps
What are quinolone antibiotics?
A member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the compound 4-quinolone
What do quinolone antibiotics target?
Topoisomerase
What do type II topoisomerases convert?
Positive supercoils (over-wound) into negative supercoils (under-wound)
What do topoisomerases regulate?
Supercoiling in DNA synthesis and RNA synthesis
What do gyrase and topoisomerase IV both consist of?
Two A subunits and two B subuints
What does the B subunit do?
Carries out the nicking of DNA