Download Prescott`s Microbiology, 9th Edition Chapter 9 –Antimicrobial

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 Etest 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 -lactamase
enzymes? Explain.
Yes. Since they are chemically related to penicillin and contain the target -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).
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© 2014 by McGraw-Hill Education. This is proprietary material solely for authorized instructor use. Not authorized for sale or distribution in
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Prescott’s Microbiology, 9th Edition
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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© 2014 by McGraw-Hill Education. This is proprietary material solely for authorized instructor use. Not authorized for sale or distribution in
any manner. This document may not be copied, scanned, duplicated, forwarded, distributed, or posted on a website, in whole or part.