Antibiotic resistance in S. aureus
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Antibiotic resistance in S. aureus
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[post_date] => 2024-12-23 17:55:38
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[post_content] => Practice Passage (Question 1-6)
*This passage is the property of Khan Academy and has been reformatted into an AAMC-style interface in their entirety by MedLife Mastery. MedLife Mastery does not endorse and is not an affiliate of Khan Academy.
MLS𝐵 resistance refers to resistance to macrolide, lincosamide and streptogramin B antibiotics (referred to as the MLS𝐵 antibiotics) in Staphylococcus aureus bacteria. It results from the production of a methylating enzyme (methylase) that is encoded by erythromycin ribosome methylation (erm) genes. This enzyme installs methyl groups on bacterial ribosomal RNA (rRNA), thereby altering the ribosomal binding site of MLS𝐵 antibiotics. The enzyme can be constitutively expressed or induced by the administration of macrolides such as erythromycin, which is a strong inducer of the methylase, or clindamycin, which is a weak inducer.
Inducible resistance results from the binding of macrolides to specific upstream translational attenuator sequences, leading to changes in mRNA secondary structure that allow the coding region to be processed by ribosomes. In constitutive resistance, alterations to upstream attenuator sequences – including deletions, duplications, and other mutations – lead to constitutive expression of the methylase gene.An in vitro test for inducible MLS𝐵 resistance is the “D test”. In this test, erythromycin- and clindamycin-impregnated disks are placed 15–20 mm apart on a “lawn” of S. aureus. In a positive D test, the zone of clearance (the area of inhibited bacterial growth) around the disk is blunted, creating a D shape (Figure 1).
Figure 1 Negative and positive clindamycin D tests
Researchers performed a D test on 100 distinct clinical isolates of Staphylococcus aureus and observed different morphologies of the zone of clearance, as shown in Figure 2.
Figure 2 D test zone-of-clearance morphologies in six distinct staphylococcal isolates Image adapted from Steward et al. J Clin Microbiol. 2005 Apr;43(4):1716-21.
[post_title] => Antibiotic resistance in S. aureus
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[question] => What is the mechanism of antibiotic resistance in S. aureus as evidenced by a positive D test?
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[answer] => 1
[description] => Reason for Correct Answer:
According to the passage, erythromycin is a strong inducer of erm expression, whereas clindamycin is a weak inducer.
Look at what is happening in Figure 1.
As shown in Figure 1, the zone of clearance to clindamycin becomes blunted, nearest to where the erythromycin is.
A blunted zone of clearance between the erythromycin and clindamycin disks indicates that bacteria nearest to erythromycin have become inducibly resistant to clindamycin, therefore erythromycin exposure induces clindamycin resistance.
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[answers] => Array
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[0] => Array
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[each_answer] => A. Exposure of Staphylococcus aureus to erythromycin induces resistance to clindamycin
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[each_answer] => B. Exposure of Staphylococcus aureus to clindamycin induces resistance to clindamycin
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[each_answer] => C. Exposure of Staphylococcus aureus to clindamycin induces resistance to erythromycin
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[each_answer] => D. Exposure of Staphylococcus aureus to erythromycin induces resistance to erythromycin
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[1] => Array
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[quiz_unique_key] => 1403770772
[question] => In Figure 2, which D test result shows an isolate of S. aureus exhibiting no antibiotic resistance?
[value] => Array
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[answer] => 4
[description] => Reason for Correct Answer:
The “lawns” shown in Figure 2 are covered with bacteria that appear white.
A dark region (susceptibility area) surrounding the antibiotic represents bacterial death caused by the antibiotic.
The absence of a dark region indicates that bacteria are not responding to this antibiotic.
In Figure 2, image F shows full circles around the antibiotics without any D shapes or cut-offs. This suggests that this bacterial isolate is responding fully to both antibiotics and exhibits no antibiotic resistance.
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[answers] => Array
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[each_answer] => A. Image B
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[each_answer] => B. Image C
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[each_answer] => C. Image E
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[each_answer] => D. Image F
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[2] => Array
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[quiz_unique_key] => 1403770772
[question] => The researchers detected a blunted zone of clearance in 51 isolates; a double-zone of clearance in 33 isolates; and no zone of clearance in 16 isolates. The prevalence of constitutive methylase production in this population is:
[value] => Array
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[answer] => 4
[description] => Reason for Correct Answer:
A blunted zone of clearance indicates inducible, not constitutive, methylase production and antibiotic resistance.
A double zone of clearance would indicate that the organism is not resistant to either erythromycin or clindamycin, and is therefore not in possession of an inducible erm gene.
Constitutive resistance would be indicated by no zone of clearance, as seen in 16 of the 100 samples in this experiment.
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[answers] => Array
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[0] => Array
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[each_answer] => A. 86%.
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[1] => Array
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[each_answer] => B. 49%.
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[each_answer] => C. 33%.
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[each_answer] => D. 16%.
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[3] => Array
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[quiz_unique_key] => 1403770772
[question] => What is the mechanism by which macrolide binding results in inducible expression of the erm sequence?
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[answer] => 3
[description] => Reason for Correct Answer:
Paragraph 2 discusses inducible versus constitutive expression.
According to the passage, alternations in upstream attenuator sequences result in constitutive, not inducible, erm expression.
In inducible erm transcription, conformational changes occur in the mRNA structure as a result of the macrolide binding to the upstream attenuator sequence. This allows for the processing of the coding region by ribosomes, according to the passage, which would initiate translation.
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[answers] => Array
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[0] => Array
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[each_answer] => A. Activation of an inducer that increases transcription of the ermgene sequence
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[each_answer] => B. Stabilization of mRNA that prevents its degradation by nucleases in the cell
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[2] => Array
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[each_answer] => C. Changes in mRNA structure that allow for the initiation of translation
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[each_answer] => D. Alterations to upstream attenuator sequences that allow for erm gene expression
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[quiz_unique_key] => 1403770772
[question] => How does the erm gene confer antibiotic resistance?
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[answer] => 3
[description] => Reason for Correct Answer:
Paragraph 1 describes how a methylating enzyme (methylase) encoded by erm genes confers bacterial resistance to macrolide antibiotics.
It states that methylase “installs methyl groups on bacterial ribosomal RNA (rRNA), thereby altering the ribosomal binding site of MLSB antibiotics.
This effectively prevents macrolides from binding and allows bacterial protein synthesis to continue. So, you can eliminate Choices A and D.
Prokaryotic ribosomes have 23s rRNA that they carry on their 50s subunit. They do not have 60s subunits like eukaryotes do. So, Choice C is correct. Here is a comparison of prokaryotic and eukaryotic ribosomes:
Note that these differences are helpful for antibiotic development, as we can create antibiotics that bind and inhibit prokaryotic/bacterial ribosomes specifically.
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[answers] => Array
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[0] => Array
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[each_answer] => A. By inducing structural changes to 23s rRNA on the 50s ribosomal subunit, preventing bacterial protein synthesis
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[1] => Array
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[each_answer] => B. By inducing structural changes to 28s rRNA on the 60s ribosomal subunit, allowing bacterial protein synthesis to continue
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[2] => Array
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[each_answer] => C. By inducing structural changes to 23s rRNA on the 50s ribosomal subunit, preventing macrolide binding
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[each_answer] => D. By inducing structural changes to 28s rRNA on the 60s ribosomal subunit, allowing macrolide binding
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[quiz_unique_key] => 1115843717
[question] => What is a potential risk of over-utilizing clindamycin in infections caused by staphylococci?
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[answer] => 1
[description] => Reason for Correct Answer:
Overuse of clindamycin can lead to preferential killing of bacteria that are sensitive to it, with the selection of bacteria that are resistant.
According to the passage, methylase enzymes can methylate bacterial ribosomal RNA and prevent clindamycin from binding.
Bacteria that constitutively express methylase enzymes or can induce their expression in response to clindamycin exposure (inducible methylase producers) can survive the antibiotic treatment, leading to the selection of these resistant strains when clindamycin is overused.
Accordingly, clindamycin use would select for bacteria that are inducible and constitutive methylase producers, killing the other bacteria that don’t express methylase.
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[each_answer] => A. It will select for inducible and constitutive methylase producers.
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[each_answer] => B. It will select for methylase nonproducers.
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[each_answer] => C. It will only kill inducible methylase producers.
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[each_answer] => D. It will only kill constitutive methylase producers.
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[554581|1] => A
[554581|2] => D
[554581|3] => D
[554581|4] => C
[554581|5] => C
[554581|6] => A
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