Flashcards in Peptidoglycan Synthesis and Major Antibiotics Deck (60):
Regarding case 4, the patient presents with sudden onset high fever. He'd had the flu over the last 3 days. What is the significance of the high fever? What is the significance of his blood pressure being recorded as 60/0?
High fever - bacterial cause
60/0 BP - TSS or similar antigen causing shock
What is a macular erythroderma? What is the significance of the patient's sore throat with cough?
Flat red rash
Staph or strep infection
What were the 3 likely diagnosis for the patient based on the presenting symptoms? Which ended up being correct?
Septic shock due to gram-positive or gram negative
Staphylococcal toxic shock syndrome following
influenza *** (Correct)***
Streptococcal toxic shock syndrome
Why was the patient administered fluids and electrolytes? Why was ceftriaxone the first drug used despite not knowing the result of the throat cultures?
Fluids and electrolytes to stabilize blood pressure
Ceftriaxone provides broad coverage for gram positive and negative bacteria
Regarding case 4, what was the pathogenic organism? What was the new diagnosis? How was the pathogenic organism classified and what new drug was used to treat the patient?
S. Aureus necrotizing pneumonia
Community acquired MRSA
What is the drug class that ceftriaxone belongs to? Why was it unable to treat the patients pathogen? What other drug class would have been similarly unsuccessful?
Because Cephalosporins can't treat MRSA
What was the specific strain of MRSA in case 4? What is the virulence factor associated with this strain?
CA MRSA USA400 strain
High levels of superantigen (enterotoxin C)
Based on the case, what were the 2 mistakes made regarding the patient's treatment?
Not using vancomycin immediately
Not using IVIG to neutralize the superantigen
What is the downside of vancomycin overuse? What is the downside of IVIG treatment?
Increase chance of resistance
IVIG is expensive
What is the function of the peptidoglycan layer? What are the 2 types of linkages found in the peptidoglycan wall? What happens if the bacteria don't have their peptidoglycan walls?
Provide strength and rigidity to bacterial cells
Glycosidic and peptide linkages
Bacteria lyse due to turgor pressure
When does peptidoglycan synthesis occur? What types of cells have peptidoglycans?
During cell division (binary fission)
Only bacterial cells
Differentiating between gram negative and positives, which will have peptidoglycan that is partially covalently bound to lipoproteins?
Gram negative - partially covalently bound insinuates decreased cross linking, a property of gram negative cell wall
Differentiating between gram negative and positives, who has thinner peptidoglycan layers? Where are the gram negative peptidoglycan layer found?
Thinner in gram negative
Found in the periplasm
What are gram positive peptidoglycans linked to (3)? Are they more or less crosslinked than gram negatives?
Techoic acids, proteins and to itself
More (75% vs. 25%)
What are the 2 major components of peptidoglycan? What is the type of bond that links these components?
N-acetyl muramic acid and N-acetylglucosamine
Beta-1,4, glycosidic bonds
What is the difference between N-acetyl muramic acid and N-acetylglucosamine?
N-acetylglucosamine plus a lactyl on carbon 3 forms N-acetyl muramc acid
N-acetyl muramic acid and N-acetylglucosamine; which has a tetrapeptide with alternating L- and D-amino acids through the lactyl groups? How are these tetrapeptides linked to each other? In other words, which moiety works to bind adjacent chains?
N-acetyl muramic acid
What is special about the D-amino acids found on the tetrapeptide in N-acetyl muramic acid?
Found only in bacteria
The tetrapeptide associated with N-acetyl muramic acid is L-alanyl-D-glutamyl-L-amino acid-D-alanine. What is the significance of the 3 residue? What is it usually?
Varies with bacterial species
Usually lysine or a diaminopimelic acid
What is the residue that is often involved with crosslinking within the peptidoglycan?
A glycine, but varies with species
What is another name for phosphonomycin? What step in peptidoglycan synthesis does it block? What is the mechanism?
Blocks the conversion of UDP-NAG to UDP-NAM
It is a phosphoenonol pyruvate analogue, a molecule necessary for that conversion
At what step in peptidoglycan synthesis does D-cycloserine work? What is the mechanism? What disease it is specifically used to treat?
It prevents the addition of D-alanine as a dipeptide to the UDP-NAP-(3AA) molecule
Blocks the enzymes responsible for those steps by acting as an analogue of L-Ala
In what cellular compartment do phosphonomycin and D-cycloserine work?
In the cytoplasm
To transition from the cytosol to the cell membrane in peptidoglycan synthesis, UDP-NAM-(Pentapeptide) becomes _. What is the cell wall precursor?
BPP-NAM - (NAG)-(peptapeptide)
What is the mechanism by which bacitracin works? What is BP? BPP? What is its function?
It prevents the conversion of BPP to BP. BPP is a required component of the cell wall precursor
BP - undecaprenol phosphate
BPP - Undecaprenol pyrophosphate (2 phosphates)
It is a lipid carrier
What is a specific example of a pathogenic microbe that is sensitive to bacitracin?
Group A strep
In what cellular compartment does bacitracin work?
It works in the inner cell membrane
In what cellular compartment does vancomycin, penicillin an dthe cephalosporins work?
The work in the exterior of the cell or in the periplasm
What is the mechanism by which vancomycin works?
It binds the 2 D-ala molecules, preventing the cross brigding to the existing cell wall
What is the mechanism by which the penicillins and cephalosporins work? As a group, penicillins and cephalosporins are known as _
The bind penicillin binding proteins, thereby blocking the transpeptidation reaction
How many PBPs does e. coli have? What about S. Aureus? Why the difference?
E. coli - 6
S. Aureus - 4
Rods will tend to have more PBPs
What are the 5 antibiotics / groups of antibiotics that target the peptidoglycan?
Wht are the 4 component groups of the beta lactams?
What occurs when the peptidoglycan cell was is ruptured? How can this be accomplished in the laboratory? WHat is the mechanism?
The bacterial cell lyses
Treating with lysozymes
Lysozyme hydrolyzes glycosidic linkages
As a rule, lysozyme is ineffective against what type of bacteria?
What types of bacteria should peptidoglycan targeting antibiotics not be used against? Why? (3)
Mycoplasma - no cell wall
Mycobacterium and chlamydia - Cell walls not suceptible
Why is PEP required for synthesis of peptidoglycan? What drug mimics it?
Needed to attach UPD for the first muramic acid.
What is the mechanism of cycloserine?
Blocks 2 enxymes (racemase and synthetase) that make the D-alanine dipeptide, the last 2 components of the peptapeptide
What is the mechanism of vancomycin?
Blocks the transpeptidation cross linking reaction
What is the mechanism of bacitracin? What specific bacteria are 10X more sensitive to this bacteria?
Prevents the regeneration of the undecaprenol phosphate from the undecaprenol pyrophosphate (blocks the pyrophosphatase)
Group A strep
What enzymes are able to cleave beta lactams? Where? How do beta lactam differ?
Cleave next to the N (left) of the 4 membered ring
Different R groups
Clavulanic acid has no antibiotic activity. What is it used for? What is the name?
It inactivates the betalactamases
Used in combo with amoxicillin as Augmentin
What is the beta lactam what is not formed by 2 rings, but rather a single 4 membered ring?
Cepahalosporin are composed of what 2 types of rings?
A 4 member and a 6 membered ring
What moiety makes beta lactams reactive with humans? What 3 betalactams have this moiety?
The sulfur group
Penicillins, Carbepenems and cephalosporins
What is the function of the penicillin binidng proteins? What drug class binds these PBPs? What is the effect of PBP inhibition?
PBPs mediate the transpeptidatio reaction on the cell wall
Inhibiton leads to cell wall destabilization
How is betalactam resistance conferred? What is it encoded by?
Expession of PBP2a (vs PBP2)
A transferrable DNA element (SCCmec DNA)
What are the 3 beta lactamase sensitive penicillins?
Benzyl penicillin (penicillin G)
Phenoxymethyl penicillin (penicillin V)
What are the 6 penicillinase reistant penicillins?
What are the 3 moderate spectrum penicillins?
What is the 1 broad spectrum penicillin? What are the 2 extended spectrum penicillins?
Broad - Augmentin
ES - Carbenicillin and Ticarcillin
What is the added effect of the extended spectrum penicillins?
They work against pseudomonas
What are the 3 first generation cephalosporins?
What are the 3 second generation cephalosporins? What is their advantage?
Add anti haemophilus activity (gram -)
What are the 2 2nd generation cephamycins with anti-anaerobe activity?
Cefotetan and cefoxitin
What are rge 3 broad spectrum cephalosporins/ Which has antipseudomonas activity?
Ceftazimide (antipseudomonas activity)
What are the 2 4th gen.cephalosporins? What is their advantage?
- enhanced gram + activity. increased beta lactamase stability
What is the example of the carbepenem provided? What is its advantage?
Broadest spectrum of beta lactams
What is the example of the monobactam provided? What is its advantage?
Reduced probability of cross sensitivity