Exam 1 - Cushman (Lecture 1) Flashcards
Describe the differences in gram (-) and (+) bacteria as it relates to drug PENETRATION of cell membrane.
In gram (+) bacteria (like cocci), drugs can penetrate the outer layers of the cell wall effectively, and the bacterial membrane is the main barrier keeping drug out of the cell.
In gram (-) bacteria, the outer membrane excludes drugs, but some can still get through the outer membrane via porins.
Describe the differences in gram (-) and (+) bacteria as it relates to BETA-LACTAMASES.
In gram (+) bacteria, B-Lactamases are excreted through the cell wall to the external environment.
In gram (-) bacteria, the B-Lacatmases are confined to the periplasmic space.
This means that the B-lactamases in gram (+) must be produced in higher quantities since they don’t have that confined space to keep them in (double layer walls).
the peptidoglycan layer is thicker in the gram (-/+) cell wall
+
gram (-/+) have a more complex cell wall. Why?
(-), Due to having an outer and inner membrane and being more lipoidal.
color differences in gram (-) or (+) bacteria in gram stain
When stained, gram (+) bacteria are dark purple, Gram (-) are pink.
what is Beta-lactamase
a resistance mechanism (enzymes) in gram (-) and (+) bacteria. They hydrolyze the beta lactam ring of beta lactam antibiotics, making them ineffective.
gram (-) peptidoglycan contains ____ residue
meso-diaminopimelic acid (DAP)
gram (+), peptidoglycan DAP is replaced by _____ residue
L-lysine (the COOH of DAP is replaced by H)
In gram (-) cells, the peptidoglycan is cross-linked by a bridge between what two parts?
the DAP residue of one strand and the terminal D-Ala of another
In gram (+) cells, the peptidoglycan is cross-linked by a bridge between what two parts?
the L-Lys strand and the D-Ala terminal of the second molecule
instability of B-Lactams is due to _____ ______
angle strain (4 member ring)
B-Lactam antibiotic mechanism of action
Inhibits transpeptidases that “glue” the peptidoglycan strands together by cross-linking. This results in an ineffective cell wall which leads to osmotic stress, resulting in cell lysis and cell death
structure of B-lactam antibiotics are similar to the ______________ fragment that is acted on by the transpeptidases, so the B-lactams fool the transpeptidases into thinking that they are the __________ fragment
D-Ala-D-Ala
Name some general resistance mechanisms to B-lactam antibiotics
-decreased cellular uptake of drug
-mutation of the penicillin-binding proteins to decrease their affinity for penicillins
-presence of efflux pump that pumps antibiotic out of the cell
B-lactamases chemically react with peptide molecule in H2O to create _______ _________
hydrolyzed penicillin
-reason for cross-reactivity in other B-lactams and penicillins
hydrolysis of B-lactam is (reversible/irreversible)
irreversible, the ring will not close back once opened
which is more protein bound and why?
ampicillin or benzylpenicillin (Pen G)
benzylpenicillin (Pen G) because it has a more lipophilic side chain
purpose of administering probenecid with a penicillin
competes for tubular secretion route and therefore increases half life of the penicillins
does benzylpenicillin (Pen G) have B-Lactamase sensitivity?
yes
benzylpenicillin (Pen G) antimicrobial spectrum
gram (+) cocci
main difference between Pen G and V?
Pen V is more stable in acid (allows better oral admin)
does methicillin have B-Lactamase sensitivity?
no
methicillin is (stable/unstable) at stomach pH
unstable, must give IV
why is methicillin discontinued?
-many bacteria are resistant to it
-MRSA exists due to a gene called mecA coding for a mutation in a penicillin binding protein (transpeptidase)
-the penicillin binding protein that it codes for is called PBP2A
