Glycopeptide Antibiotics Presentation

Glycopeptide Antibiotics

By Nikitha, Charlotte, Talia, and Emma

What are

glycopeptides?

❖

Large, rigid molecules

❖

Selectively toxic with
hydrogen bonding

❖

Act against gram-positive
bacteria (i.e. those with a
peptidoglycan cell wall)

Multiple Choice

What kinds of bacterial infections do glycopeptide antibiotics treat?

• gram-positive bacteria

• gram-negative bacteria

What does it mean for bacteria to be
gram-positive?

❖

Gram stain determines what kind of cell wall the bacteria has
➢

positive/negative is determined by whether the bacteria retains the
violet stain

Many peptidoglycans joined
together

Multiple Choice

What is the difference between gram-positive and gram-negative bacteria?

• gram-pos = heavier membrane

  gram-neg = lighter membrane

• gram-pos = genetically modified

  gram-neg = not GMO

• gram-pos = peptidoglycan layers

  gram-neg = no peptidoglycan layers

• gram-pos = only peptidoglycan layers

  gram-neg = yes outer membrane, only 1 peptidoglycan layer

How and where were glycopeptides
discovered?

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Discovered in the 1950s

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First glycopeptide antibiotics that were
discovered were Vancomycin 1 and Ristocetin 2

❖

Developed to treat MRSA (Staphylococcus
aureus), which is resistant to penicillin

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Vancomycin discovered in a strain of
Amycolatopsis orientalis on Borneo

❖

Excessive use of vancomycin has resulted in
numerous strains of vancomycin-resistant
enterococci (VRE)

Fig 1: Amycolaptosis orientalis

Fig 2 : Vancomycin’s chemical structure

Multiple Choice

Against what disease were glycopeptide antibiotics developed to treat and why?

• E. coli, because it's typically found plant-based foods with cell walls

• Strep, because it's penicillin-resistant

• MRSA, because it's penicillin-resistant

• Meningitis, because it requires selective treatments

How do glycopeptides work to kill bacteria?

https://youtu.be/BbtwNNe-lp4?t=311a ~ animation of vancomycin (type of glycopeptide antibiotic)

Multiple Choice

What part of bacteria do glycopeptide antibiotics target?

• protein synthesis

• cell wall synthesis

• plasma membrane

• essential metabolite synthesis

Multiple Choice

How does vancomycin (a glycopeptide antibiotic) work to disrupt the bacteria's cell wall synthesis?

• acts as "molecular scissors" to cut the linkages of the peptidoglycan layer

• prevents the cross-linking that binds the two peptide chains by noncompetitive inhibition, with vancomycin changing the shape of peptide residues

• interferes with the production of cell wall proteins

• prevents the cross-linking that binds the two peptide chains via competitive inhibition, binding to the residues itself

Developing

Resistance to
Vancomycin

https://youtu.be/BbtwNNe-lp4?t=365

Multiple Choice

How did some enterococcal bacteria develop resistance to vancomycin?

• overprescription of vancomycin

• all of the above

• people not finishing their dosages of vancomycin

• exposure to other antibiotics with activity against anaerobic bacteria

Multiple Choice

What adaptation did enterococcal bacteria evolve to have in order to evade vancomycin?

• different residues on the peptide chains that prevent vancomycin from inhibiting their cross-linking

• changed the constitution of their cell wall to have different peptides that don't require cross-linking

• stronger peptide chains that out-compete vancomycin

• an outer membrane surrounding their peptidoglycan layers, preventing vancomycin from entering the bacteria

What are some ways to treat VRE?

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VRE = Vancomycin-resistant
enterococci

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Work in progress, first documented case of VRE was in 1988
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Membrane Targeting

➢

Backbone Modifications

➢

Hybridizing

Multiple Select

What are some ways to treat VRE?

• engineer vancomycin to prevent the synthesis of cell wall proteins

• stop prescribing vancomycin to patients who don't listen

• backbone modifications

• membrane targeting

Sources

1.

https://www.drugs.com/drug-class/glycopeptide-antibiotics.html

2.

https://biologydictionary.net/peptidoglycan/

3.

https://pubmed.ncbi.nlm.nih.gov/33470191/

4.

https://www.sciencedirect.com/science/article/pii/B9780080453828001933

5.

https://link.springer.com/article/10.1007/BF01967563

6.

https://www.researchgate.net/figure/Structures-of-glycopeptides-used-in-our-study_fig2_2
32721257

7.

https://synapse.koreamed.org/upload/SynapseData/PDFData/0079jbv/jbv-45-67.pdf

8.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952257/

9.

https://www.nature.com/articles/ja2013117

10.

https://www.youtube.com/watch?v=7SVGwiA7AyI&ab_channel=PharmacologyAnimation

11.

https://www.youtube.com/watch?v=fOCXqYYDCqA&ab_channel=DrMatt%26DrMike

12.

https://www.youtube.com/watch?v=BbtwNNe-lp4&ab_channel=MichaelDobson