Instructor Notes — Chapter 25

Antimicrobial Peptides: The Natural Weapons That Could Solve Antibiotic Resistance Part 5 opener · advanced · prerequisites Chapters 2, 5, 4 · estimated 6–8 hours

What this chapter is really teaching

The surface content is antimicrobial peptides. The actual pedagogical payload is how to write a verdict when there is no verdict, and Chapter 25 is where the book's fourth rating stops being a definition and becomes a skill.

Everything else in the chapter is scaffolding for that. The resistance burden teaches precision about a headline number. The mechanism teaches the difference between a real advantage and an absolute one. The selectivity problem supplies a concrete, physical obstacle that no amount of enthusiasm dissolves. The economics supply a second obstacle of an entirely different kind. And §25.8 supplies the correction that prevents students from collapsing "no verdict" into "failure."

If you have limited time, teach §25.5, §25.8, and §25.9. The rest can be assigned.

The three moments students reliably get wrong

1. They upgrade the resistance argument. Almost every student, and a majority of the popular sources they will have read, converts "resistance is harder to evolve" into "resistance cannot evolve." This is the chapter's designated hype risk and it is worth spending real class time on, because it is a general failure mode: a quantitative advantage being upgraded to a qualitative one because the qualitative version is more quotable. mcr is the fact that stops it, and it is worth making students say out loud what mcr does and does not prove.

2. They read ✅ as an endorsement. The colistin rating is deliberately placed to break this. Some students will insist the rating is wrong because the drug is toxic. Do not resolve this quickly — it is the most productive confusion in the chapter. The resolution is that ✅ assesses evidence for a stated claim, and "colistin treats these infections" is a well-supported claim about a drug nobody enjoys receiving.

3. They treat 🔬 as a mild ✅. Students hear "frontier" as "nearly there." The failure-modes subsection at the end of §25.9 addresses this directly, but it needs reinforcing: most compounds at the frontier do not arrive, and a 🔬 with forty years of unsuccessful programs behind it is a different object from a 🔬 on a compound that entered trials last year.

Suggested class structure (single 90-minute session)

0–10 min. Open with the number. Write "1.27 million" and "4.95 million" on the board and ask which is the death toll of antibiotic resistance. Let the disagreement run before resolving it.

10–25 min. Mechanism, fast. The goal is not memorizing three pore models; it is the single sentence the thing being attacked is a bulk physical structure, not a molecule with a binding site, and its consequence for resistance.

25–40 min. mcr. Present it as a puzzle: given what we just said about membranes being hard to redesign, how did this happen? Students who work out that charge modification is a surface change rather than a structural one have understood the mechanism properly.

40–60 min. Selectivity. This is the heart. Use the invented selectivity index arithmetic on the board — two peptides, identical MICs, different futures — and ask which number a press release would lead with.

60–75 min. The reveal. Ask how many peptide antibiotics are currently approved. Most classes guess zero or one. Then list them. This moment does more for students' skepticism about their own prior reading than anything you can say.

75–90 min. The 🔬. Write the rating on the board without its "what would change it" line, and ask whether it is a rating or a shrug. Then have students supply the missing line.

Assessment notes

  • Exercise L† (Chapter 2 contrast) is the best single essay prompt in the chapter and works well as a take-home.
  • Exercise AF† (write it optimistically, write it pessimistically, neither may contain a false statement) is the highest-yield exercise for teaching rhetorical awareness. Budget class time to discuss the third paragraph, where students name their own techniques.
  • Exercise AB† requires students to take a policy position the book refuses to take. Make clear that they are being graded on the quality of the self-objection, not on the position.
  • Spaced Review Q5 doubles as a compact exam question; it tests the whole dossier apparatus in 150 words.
  • The quiz answer key is published to students in quiz.md. The full answer set for exercises is in _scratch/answers/ch25.md and should not be distributed.

Common factual errors to correct proactively

  • "Vancomycin is a membrane-disrupting peptide." It is a peptide; its mechanism is cell wall precursor binding. The chapter says "peptide antibiotic" describes composition, not mechanism.
  • "Daptomycin doesn't reach the lung." It reaches the lung and is inactivated there by surfactant. The distinction matters, and it is a Chapter 4 idea.
  • "Defensins are found only in humans." Defensin-type peptides are widespread; the α/β split described is the human one.
  • "AMPs are all α-helical." Defensins are β-sheet. The α-helical case dominates teaching because magainins were the model system.
  • "Colistin was withdrawn." It was largely abandoned in practice, not withdrawn from approval.

Safety and framing note

Students sometimes leave a session on antimicrobial peptides interested in "natural antimicrobials" as a personal health topic. Be explicit: this chapter contains no guidance about treating infection, untreated bacterial infection is a medical emergency, and the mechanism that makes these molecules interesting is indiscriminate membrane damage with a margin narrow enough to have defeated well-funded clinical programs. The §25.5 🩺 callout is the text to point at.