Peptidoglycan Synthesis and Major Antibiotics Flashcards

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
Q

What is the mechanism by which bacitracin works? What is BP? BPP? What is its function?

A

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
Q

What is a specific example of a pathogenic microbe that is sensitive to bacitracin?

A

Group A strep

27
Q

In what cellular compartment does bacitracin work?

A

It works in the inner cell membrane

28
Q

In what cellular compartment does vancomycin, penicillin an dthe cephalosporins work?

A

The work in the exterior of the cell or in the periplasm

29
Q

What is the mechanism by which vancomycin works?

A

It binds the 2 D-ala molecules, preventing the cross brigding to the existing cell wall

30
Q

What is the mechanism by which the penicillins and cephalosporins work? As a group, penicillins and cephalosporins are known as _

A

The bind penicillin binding proteins, thereby blocking the transpeptidation reaction
Beta lactams

31
Q

How many PBPs does e. coli have? What about S. Aureus? Why the difference?

A

E. coli - 6
S. Aureus - 4
Rods will tend to have more PBPs

32
Q

What are the 5 antibiotics / groups of antibiotics that target the peptidoglycan?

A
Phosphonomycin 
Cycloserine
Vancomycin 
Bacitracin 
Beta lactams
33
Q

Wht are the 4 component groups of the beta lactams?

A

Penicillins
Cephalosporins
Monobactams
Carbapenems

34
Q

What occurs when the peptidoglycan cell was is ruptured? How can this be accomplished in the laboratory? WHat is the mechanism?

A

The bacterial cell lyses
Treating with lysozymes
Lysozyme hydrolyzes glycosidic linkages

35
Q

As a rule, lysozyme is ineffective against what type of bacteria?

A

Pathogenic bacteria

36
Q

What types of bacteria should peptidoglycan targeting antibiotics not be used against? Why? (3)

A

Mycoplasma - no cell wall

Mycobacterium and chlamydia - Cell walls not suceptible

37
Q

Why is PEP required for synthesis of peptidoglycan? What drug mimics it?

A

Needed to attach UPD for the first muramic acid.

Phsphonomycin

38
Q

What is the mechanism of cycloserine?

A

Blocks 2 enxymes (racemase and synthetase) that make the D-alanine dipeptide, the last 2 components of the peptapeptide

39
Q

What is the mechanism of vancomycin?

A

Blocks the transpeptidation cross linking reaction

40
Q

What is the mechanism of bacitracin? What specific bacteria are 10X more sensitive to this bacteria?

A

Prevents the regeneration of the undecaprenol phosphate from the undecaprenol pyrophosphate (blocks the pyrophosphatase)
Group A strep

41
Q

What enzymes are able to cleave beta lactams? Where? How do beta lactam differ?

A

Beta lactamases
Cleave next to the N (left) of the 4 membered ring
Different R groups

42
Q

Clavulanic acid has no antibiotic activity. What is it used for? What is the name?

A

It inactivates the betalactamases

Used in combo with amoxicillin as Augmentin

43
Q

What is the beta lactam what is not formed by 2 rings, but rather a single 4 membered ring?

A

Monobactams

44
Q

Cepahalosporin are composed of what 2 types of rings?

A

A 4 member and a 6 membered ring

45
Q

What moiety makes beta lactams reactive with humans? What 3 betalactams have this moiety?

A

The sulfur group

Penicillins, Carbepenems and cephalosporins

46
Q

What is the function of the penicillin binidng proteins? What drug class binds these PBPs? What is the effect of PBP inhibition?

A

PBPs mediate the transpeptidatio reaction on the cell wall
Beta lactams
Inhibiton leads to cell wall destabilization

47
Q

How is betalactam resistance conferred? What is it encoded by?

A

Expession of PBP2a (vs PBP2)

A transferrable DNA element (SCCmec DNA)

48
Q

What are the 3 beta lactamase sensitive penicillins?

A

Benzyl penicillin (penicillin G)

Phenoxymethyl penicillin (penicillin V)

Procaine penicillin

49
Q

What are the 6 penicillinase reistant penicillins?

A
Methicillin
Oxacillin
Nafcillin
Cloxacillin
Dicloxacillin
Flucloxacillin
50
Q

What are the 3 moderate spectrum penicillins?

A

Amoxacillin
Ampicillin
Piperacillin

51
Q

What is the 1 broad spectrum penicillin? What are the 2 extended spectrum penicillins?

A

Broad - Augmentin

ES - Carbenicillin and Ticarcillin

52
Q

What is the added effect of the extended spectrum penicillins?

A

They work against pseudomonas

53
Q

What are the 3 first generation cephalosporins?

A

Cefalexin
Cephalothin
Cephazolin

54
Q

What are the 3 second generation cephalosporins? What is their advantage?

A

Cefaclor
Cefuroxime
Cefamandole
Add anti haemophilus activity (gram -)

55
Q

What are the 2 2nd generation cephamycins with anti-anaerobe activity?

A

Cefotetan and cefoxitin

56
Q

What are rge 3 broad spectrum cephalosporins/ Which has antipseudomonas activity?

A

Ceftriaxone
Cefotaxime
Ceftazimide (antipseudomonas activity)

57
Q

What are the 2 4th gen.cephalosporins? What is their advantage?

A

Cefipime
Cefpirome
- enhanced gram + activity. increased beta lactamase stability

58
Q

What is the example of the carbepenem provided? What is its advantage?

A

Imipenem

Broadest spectrum of beta lactams

59
Q

What is the example of the monobactam provided? What is its advantage?

A

Aztreonam

Reduced probability of cross sensitivity

60
Q

What are the 3 beta lactamase inhibitors provided?

A

Clavulanic acid
Tazobactam
Sulbactam