• What is antibiotic resistance?

• A brief history of antibiotics and resistance:

Worksheet by: Federico Prokopczuk (Discussion Leader) & Gilberto Mendez

• Why is it such a major problem?

• How does it develop and spread?

Discussion PointsDiscovery of Next-Generation Antimicrobials through

Bacteria Self-Screening of Surface-Displayed Peptide Libraries

Article DOI: 10.1016/j.cell.2017.12.009.

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DIRECTIONS Today we will discuss a primary research article using this worksheet as a discussion guide. You will be assigned a partner and one of the 13 discussion points listed below. You will have 20-minutesto evaluate your assigned point(s) with your partner. The discussion will then start and each

group will be able to share their thoughts as we go over each section of the review article.

1) Set up the big picture. Why is this work significant? In your discussion include and expand on the information/questions listed below using your own words.

2) What is the biological system under review in this paper? In your discussion include and expand on the information/questions listed below using your own words.

3) Previous methods of screening: The paper mentions some common methods used for screening.In your discussion expand on the question listed below.

4) The SLAY system: Use Figure 1 (A), describe the four components of the SLAY system and their functions.

5) Bacterial activity of the SLAY system: Describe Figure 1 (B-D). In your discussion include and expand on the questions listed below.

6) Functionality of SLAY system: Describe Figure 1 (E-G). In your discussion include and expand on the question listed below.

7) SLAY screening system: Use Figure 2 to describe the methodology of the SLAY screening system.

8) SLAY platform with a small defined library: Describe the experiment in Figure 3. In your discussion include and expand on the question listed below.

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• What are antimicrobial peptides (AMP)?

• How do AMPS differ from traditional antibiotics?

• What are AMPs common mechanism of action?

• Define these methods: Phage display and chemical synthesis.

• What are the pros and cons of the two methods above?

• What does Figure 1 (D) tell us about the functionality of the system?

• What does Figure 1 (G) tell us about mixed culture experiments?

• What does this figure tell us about the functionality of the system?

• How do you read these plots?

• The two major types of bacteral envelopes: • Selectivity of AMPs:

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9) Random peptides library results: Explain Figure 4 (A-D). In your discussion include and expand on the questions listed below.

• How did the researchers screen so many peptides at once?

• What is surprising in regards to the active peptides found as compared to known naturally occuring AMPs?

• How does this compliment or detract from the data represented in Figure 4.

10) Antimicrobial activity of peptides: Using Table 2, describe the experiments performed. In your discussion include and expand on the questions listed below.

11) False positives: The paper describes occurences of some false positives coming through in the SLAY methods, but not in the MBC tests. Discuss some reasons this could happen.

References:

• Tackling Antimicrobial Resistance. (2014). Retrieved March 12, 2018, from http://www.rcuk.ac.uk/research/xrcprogrammes/tackling-antimicrobial-resistance/

• Wiring Diagram - Everything You Need to Know About Wiring Diagram Just another WordPress site. (n.d.). Retrieved March 12, 2018, from http://collagenrrestores.com/diagram-of-bacteria-photo/bacteria-video-prokaryote-structure-khan-academy-4/

• World Antibiotic Awareness Week – How much do you know about antibiotic resistance? (2012, July 2). Retrieved March 12, 2018, from http://patienttalk.org/tag/antibiotic-resistance/

12) Mechanism and toxicity: Use Figure 5 to discuss the mechanism of the screened peptides. How does this relate to toxicity?

13) Significance: Summarize the discussion from the paper.