Peptidoglycan Synthesis and Major Antibiotics Flashcards

(60 cards)

1
Q

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?

A

High fever - bacterial cause

60/0 BP - TSS or similar antigen causing shock

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2
Q

What is a macular erythroderma? What is the significance of the patient’s sore throat with cough?

A

Flat red rash

Staph or strep infection

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3
Q

What were the 3 likely diagnosis for the patient based on the presenting symptoms? Which ended up being correct?

A

Septic shock due to gram-positive or gram negative
bacteria
Staphylococcal toxic shock syndrome following
influenza * (Correct)*
Streptococcal toxic shock syndrome

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4
Q

Why was the patient administered fluids and electrolytes? Why was ceftriaxone the first drug used despite not knowing the result of the throat cultures?

A

Fluids and electrolytes to stabilize blood pressure

Ceftriaxone provides broad coverage for gram positive and negative bacteria

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5
Q

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?

A

Staph. aureus
S. Aureus necrotizing pneumonia
Community acquired MRSA
Vancomycin

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6
Q

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?

A

Cephalosporin
Because Cephalosporins can’t treat MRSA
Penicillins

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7
Q

What was the specific strain of MRSA in case 4? What is the virulence factor associated with this strain?

A

CA MRSA USA400 strain

High levels of superantigen (enterotoxin C)

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8
Q

Based on the case, what were the 2 mistakes made regarding the patient’s treatment?

A

Not using vancomycin immediately

Not using IVIG to neutralize the superantigen

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9
Q

What is the downside of vancomycin overuse? What is the downside of IVIG treatment?

A

Increase chance of resistance

IVIG is expensive

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10
Q

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?

A

Provide strength and rigidity to bacterial cells
Glycosidic and peptide linkages
Bacteria lyse due to turgor pressure

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11
Q

When does peptidoglycan synthesis occur? What types of cells have peptidoglycans?

A

During cell division (binary fission)

Only bacterial cells

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12
Q

Differentiating between gram negative and positives, which will have peptidoglycan that is partially covalently bound to lipoproteins?

A

Gram negative - partially covalently bound insinuates decreased cross linking, a property of gram negative cell wall

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13
Q

Differentiating between gram negative and positives, who has thinner peptidoglycan layers? Where are the gram negative peptidoglycan layer found?

A

Thinner in gram negative

Found in the periplasm

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14
Q

What are gram positive peptidoglycans linked to (3)? Are they more or less crosslinked than gram negatives?

A

Techoic acids, proteins and to itself

More (75% vs. 25%)

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15
Q

What are the 2 major components of peptidoglycan? What is the type of bond that links these components?

A

N-acetyl muramic acid and N-acetylglucosamine

Beta-1,4, glycosidic bonds

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16
Q

What is the difference between N-acetyl muramic acid and N-acetylglucosamine?

A

N-acetylglucosamine plus a lactyl on carbon 3 forms N-acetyl muramc acid

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17
Q

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?

A

N-acetyl muramic acid

Peptide bonds

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18
Q

What is special about the D-amino acids found on the tetrapeptide in N-acetyl muramic acid?

A

Found only in bacteria

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19
Q

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?

A

Varies with bacterial species

Usually lysine or a diaminopimelic acid

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20
Q

What is the residue that is often involved with crosslinking within the peptidoglycan?

A

A glycine, but varies with species

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21
Q

What is another name for phosphonomycin? What step in peptidoglycan synthesis does it block? What is the mechanism?

A

Fosfomycin
Blocks the conversion of UDP-NAG to UDP-NAM
It is a phosphoenonol pyruvate analogue, a molecule necessary for that conversion

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22
Q

At what step in peptidoglycan synthesis does D-cycloserine work? What is the mechanism? What disease it is specifically used to treat?

A

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
Tuberculosis

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23
Q

In what cellular compartment do phosphonomycin and D-cycloserine work?

A

In the cytoplasm

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24
Q

To transition from the cytosol to the cell membrane in peptidoglycan synthesis, UDP-NAM-(Pentapeptide) becomes _. What is the cell wall precursor?

A

BPP-NAM-(peptapeptide)

BPP-NAM - (NAG)-(peptapeptide)

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25
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
26
What is a specific example of a pathogenic microbe that is sensitive to bacitracin?
Group A strep
27
In what cellular compartment does bacitracin work?
It works in the inner cell membrane
28
In what cellular compartment does vancomycin, penicillin an dthe cephalosporins work?
The work in the exterior of the cell or in the periplasm
29
What is the mechanism by which vancomycin works?
It binds the 2 D-ala molecules, preventing the cross brigding to the existing cell wall
30
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 Beta lactams
31
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
32
What are the 5 antibiotics / groups of antibiotics that target the peptidoglycan?
``` Phosphonomycin Cycloserine Vancomycin Bacitracin Beta lactams ```
33
Wht are the 4 component groups of the beta lactams?
Penicillins Cephalosporins Monobactams Carbapenems
34
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
35
As a rule, lysozyme is ineffective against what type of bacteria?
Pathogenic bacteria
36
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
37
Why is PEP required for synthesis of peptidoglycan? What drug mimics it?
Needed to attach UPD for the first muramic acid. | Phsphonomycin
38
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
39
What is the mechanism of vancomycin?
Blocks the transpeptidation cross linking reaction
40
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
41
What enzymes are able to cleave beta lactams? Where? How do beta lactam differ?
Beta lactamases Cleave next to the N (left) of the 4 membered ring Different R groups
42
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
43
What is the beta lactam what is not formed by 2 rings, but rather a single 4 membered ring?
Monobactams
44
Cepahalosporin are composed of what 2 types of rings?
A 4 member and a 6 membered ring
45
What moiety makes beta lactams reactive with humans? What 3 betalactams have this moiety?
The sulfur group | Penicillins, Carbepenems and cephalosporins
46
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 Beta lactams Inhibiton leads to cell wall destabilization
47
How is betalactam resistance conferred? What is it encoded by?
Expession of PBP2a (vs PBP2) | A transferrable DNA element (SCCmec DNA)
48
What are the 3 beta lactamase sensitive penicillins?
Benzyl penicillin (penicillin G) Phenoxymethyl penicillin (penicillin V) Procaine penicillin
49
What are the 6 penicillinase reistant penicillins?
``` Methicillin Oxacillin Nafcillin Cloxacillin Dicloxacillin Flucloxacillin ```
50
What are the 3 moderate spectrum penicillins?
Amoxacillin Ampicillin Piperacillin
51
What is the 1 broad spectrum penicillin? What are the 2 extended spectrum penicillins?
Broad - Augmentin | ES - Carbenicillin and Ticarcillin
52
What is the added effect of the extended spectrum penicillins?
They work against pseudomonas
53
What are the 3 first generation cephalosporins?
Cefalexin Cephalothin Cephazolin
54
What are the 3 second generation cephalosporins? What is their advantage?
Cefaclor Cefuroxime Cefamandole Add anti haemophilus activity (gram -)
55
What are the 2 2nd generation cephamycins with anti-anaerobe activity?
Cefotetan and cefoxitin
56
What are rge 3 broad spectrum cephalosporins/ Which has antipseudomonas activity?
Ceftriaxone Cefotaxime Ceftazimide (antipseudomonas activity)
57
What are the 2 4th gen.cephalosporins? What is their advantage?
Cefipime Cefpirome - enhanced gram + activity. increased beta lactamase stability
58
What is the example of the carbepenem provided? What is its advantage?
Imipenem | Broadest spectrum of beta lactams
59
What is the example of the monobactam provided? What is its advantage?
Aztreonam | Reduced probability of cross sensitivity
60
What are the 3 beta lactamase inhibitors provided?
Clavulanic acid Tazobactam Sulbactam