Prescott’s Microbiology, 9th Edition
Chapter 9 –Antimicrobial Chemotherapy
GUIDELINES FOR ANSWERING THE MICRO INQUIRY QUESTIONS
Figure 9.4 Based on these zones of diffusion, which EtestÒ strip contains the most effective antibiotic against this microbe? Which is the least effective?
Under the growth conditions of this agar plate, the antibiotic labeled Cl has the lowest (and thus most effective) MIC, at 0.064 micrograms/ml. Make clear the point to students that this does NOT tell which drug is the most effective in a patient. Inside a patient and in vitro are very different environments. The highest MIC under these conditions was PTC, at 3.
Figure 9.5 What is the difference between penicillin G and penicillin V? How do the semisynthetic penicillins differ from their parent compounds?
Penicillin G has a phenylacetyl sidechain (highlighted in purple) and Penicillin V has a phenoxymethyl sidechain and is more resistant to acid (thus less digested in the stomach, and can be given orally, unlike G which has to be given by injection). Chemically, the semisynthetic penicillins have an enormous variety of structures, as there are hundreds of these compounds on the market as antibiotics. Because of their structures, they also vary in spectrum of activity against different bacterial species, in sensitivity to different penicillinases (lactamase enzymes), and in their pharmaceutical properties, such as oral bioavailability, serum half-life, etc.
Figure 9.6 Do you think cephalosporin antibiotics are susceptible to degradation by b-lactamase enzymes? Explain.
Yes. Since they are chemically related to penicillin and contain the target b-lactam ring, they can be degraded by lactamase enzymes. It is important to note however that these drugs are typically resistant to the early lactamase enzymes that cleave penicillin and closely related compounds, because of the large side chains that the cephalosporin antibiotics have, which is exactly why they were made.
Figure 9.8 How do these drugs inhibit protein synthesis?
Aminoglycosides bind to the 30S ribosomal subunit to interfere with protein synthesis, causing the ribosome to make errors (mistranslation). These proteins have the wrong amino acids, and thus typically do not properly fold.
Figure 9.10 How is the mechanism by which macrolides block protein synthesis similar to that of the tetracyclines? How is it different?
Both act on the ribosome, specifically on the 30S subunit. However, aminoglycosides cause tRNA mismatching leading to protein mistranslation (thus incorrect proteins are made) whereas tetracyclines bind to the 30S subunit and block tRNA entry into the ribosome A site (thus no proteins are made).
Figure 9.11 Why do sulfa drugs have a high therapeutic index?
Sulfonamides have a high therapeutic index because they block folic acid synthesis but humans lack this synthetic pathway and must obtain our folate from our diet (target a prokaryotic-specific metabolic pathway).
Figure 9.14 What is the mechanism by which nystatin inhibits growth? How does this compare to that of amphotericin B? Do you think nystatin is less toxic than amphotericin? (Hint: Think about how the two drugs are delivered.)
Nystatin binds to sterols (recall fungi have ergosterol while human cells have cholesterol, thus these polyene drugs can be somewhat selective) and damages the membrane leading to fungal membrane leakage. Amphotericin B has the same target and mechanism of action. This information the students have to acquire themselves, it is not in the text: Nystatin is orally administered in a suspension, and it stays in the GI tract because it is only poorly absorbed. It is therefore used primarily to treat GI funalg infections. It is rather well tolerated. On the other hand, amphotericin B is given IV, and can thus be used to treat systemic fungal infections. It has serious side effects, including fever, chills, hypotension, nausea, arrhythmias, and shock.
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