Antibiotic Resistance and Genetic Plasticity (2B)
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MCAT Biological and Biochemical Foundations of Living Systems › Antibiotic Resistance and Genetic Plasticity (2B)
A researcher exposes a clonal population of Mycobacterium to isoniazid. After treatment, a few colonies survive. Fluctuation testing across many parallel cultures shows high variability in the number of survivors between cultures (some have none, a few have many). Sequencing reveals a single base substitution in a gene required to activate isoniazid inside the cell. Which mechanism best explains the observed resistance?
Resistance is due to temporary phenotypic acclimation that is not tied to DNA sequence changes
Pre-existing spontaneous mutations arose before drug exposure and were selected by isoniazid treatment
Isoniazid induces the specific activating-gene mutation only after exposure, producing similar survivor counts across cultures
Resistance is explained by meiotic recombination generating new alleles in response to stress
Explanation
This question tests understanding of the Luria-Delbrück fluctuation test and pre-existing mutations in antibiotic resistance. The fluctuation test reveals whether mutations arise spontaneously before selection (producing high variance between cultures) or are induced by the selective agent (producing uniform results). The passage shows high variability in survivor numbers across parallel cultures and identifies a loss-of-function mutation in the isoniazid-activating gene. This pattern indicates that rare spontaneous mutations occurred randomly before drug exposure and were then selected by isoniazid treatment. Choice B (induced mutations) is incorrect because induced mutations would produce similar survivor counts across cultures. To distinguish spontaneous from induced mutations, examine the distribution of resistant colonies across replicate experiments.
A clinician notices that a patient’s Klebsiella isolate becomes resistant to two unrelated antibiotics during therapy. Genome sequencing reveals no new chromosomal mutations but identifies a newly acquired plasmid carrying two resistance genes. The plasmid is readily transferred to a lab strain during co-culture, but transfer is blocked when cell-to-cell contact is prevented using a membrane that allows diffusion of small molecules but not bacteria. Which mechanism best explains the observed resistance?
Transformation by uptake of naked plasmid DNA diffusing across the membrane
Transduction mediated by bacteriophages that diffuse through the membrane
Conjugation requiring direct contact to transfer a multi-resistance plasmid
Translation errors creating transient resistance proteins without genetic change
Explanation
The skill being tested is identifying conjugation as a contact-dependent resistance transfer mechanism. Conjugation involves pilus-mediated plasmid transfer between touching cells, often carrying multiple resistance genes, and is blocked by preventing contact. In this Klebsiella case, a new plasmid with two resistance genes is acquired, transferable in co-culture but not across a contact-preventing membrane. Choice A is correct as it fits the direct contact requirement for plasmid transfer. Choice B fails because transformation uses free DNA, which diffuses through the membrane, but transfer was blocked. To verify, use membrane separation experiments in similar setups. Confirm plasmids via sequencing and test for multiple resistance linkage.
A bacterium becomes resistant to rifampin, which targets bacterial RNA polymerase. Sequencing shows a single nucleotide change in rpoB (RNA polymerase beta subunit). In vitro transcription assays show normal transcription rate but rifampin no longer inhibits the enzyme. Based on the data, which genetic change is most consistent with the resistance observed?
A synonymous mutation in rpoB that reduces translation of RNA polymerase
Deletion of the rpoB gene that forces the cell to use eukaryotic RNA polymerase
A missense mutation in rpoB that alters the rifampin binding site without abolishing function
A frameshift mutation in rpoB that truncates RNA polymerase and prevents transcription
Explanation
The skill being tested is recognizing missense mutations in target genes for resistance. Missense mutations change amino acids, altering drug-binding sites in essential proteins like RNA polymerase without losing function. Here, a single rpoB nucleotide change allows normal transcription but prevents rifampin inhibition. Choice B is correct as it describes a missense mutation modifying the binding site while preserving enzyme activity. Choice C is incorrect because a frameshift would truncate and inactivate the polymerase, halting transcription. In similar analyses, classify mutation types via sequencing. Test functionality with in vitro assays to ensure viability.
A lab compares two E. coli populations exposed to the same antibiotic. Population X is grown at a single high concentration and shows few survivors. Population Y is exposed to gradually increasing concentrations over several days and becomes highly resistant. Sequencing of Population Y reveals multiple mutations, including one in the drug target. What outcome is most likely given the adaptation described?
High-dose exposure increases mutation rate in survivors in a directed way, producing identical resistant genotypes
Population Y becomes resistant because sensitive cells convert resistance proteins into DNA and pass them to offspring
Gradual exposure can allow stepwise selection of mutants with increasing resistance, leading to a more resistant population
Population Y becomes resistant because antibiotics are metabolized into mutagens that specifically edit the target gene
Explanation
The skill being tested is comparing selection strategies in resistance evolution. Gradual antibiotic exposure enables stepwise accumulation of mutations, selecting increasingly resistant variants over time. In this E. coli comparison, Population Y's gradual exposure yields highly resistant mutants with multiple changes, including in the target. Choice A is correct as it explains stepwise selection leading to greater resistance. Choice B is incorrect because mutations are not directed; high-dose survivors show fewer adaptations. For analogous experiments, sequence genomes at intervals. Assess resistance levels via MIC to quantify evolution.
A bacterium becomes resistant to an antibiotic that binds a specific cell wall enzyme. Researchers find that resistant cells produce the same amount of enzyme as sensitive cells, but the enzyme’s amino acid sequence differs by one residue. The antibiotic concentration inside the cell is unchanged. Which mechanism best explains the observed resistance?
Gene duplication of the enzyme locus, diluting the antibiotic among more targets
Acquisition of a plasmid encoding a porin that increases antibiotic efflux
A point mutation causing an amino acid substitution that lowers antibiotic binding to the enzyme
Epigenetic silencing of the enzyme gene, preventing the antibiotic from finding its target
Explanation
The skill being tested is recognizing target modification via mutation in resistance. Point mutations can substitute amino acids in enzymes, reducing antibiotic binding without changing expression or intracellular levels. Here, resistant cells have one amino acid difference in the cell wall enzyme, with unchanged production and drug concentration. Choice B is correct as it explains lowered binding via substitution. Choice A fails because enzyme amounts are the same, not duplicated. For related problems, compare protein sequences and binding affinities. Measure expression and drug levels to rule out alternatives.
A lab strain gains resistance to chloramphenicol. The resistant strain carries a new plasmid encoding an acetyltransferase that chemically modifies chloramphenicol. When the plasmid is cured (lost), the strain becomes sensitive again, and no chromosomal mutations are detected. Which outcome is most consistent with this system?
Resistance will persist because acetyltransferase activity is an irreversible environmental adaptation
Resistance will increase because plasmid loss triggers compensatory meiosis to generate resistant spores
Resistance will be lost when the plasmid is removed because the resistance determinant is plasmid-encoded
Resistance will persist because plasmid genes automatically integrate into the chromosome during curing
Explanation
The skill being tested is distinguishing plasmid-mediated from chromosomal resistance. Plasmid-encoded resistance, like acetyltransferase modifying chloramphenicol, is lost upon plasmid curing, reverting sensitivity without chromosomal changes. Here, resistance is plasmid-linked and lost after curing, with no mutations detected. Choice A is correct as it explains loss due to plasmid removal. Choice B fails because plasmids do not automatically integrate; resistance reverts. To confirm, perform plasmid curing and sensitivity tests. Sequence chromosomes to exclude mutations.
A hospital compares Pseudomonas aeruginosa isolates from two wards. Ward A uses ciprofloxacin frequently; Ward B rarely uses it. Over 6 months, ciprofloxacin-resistant isolates become common in Ward A but remain rare in Ward B. Whole-genome sequencing shows that resistant isolates in Ward A are genetically diverse (not all closely related), yet many share changes in a drug-efflux regulator that increase efflux pump activity. What outcome is most likely given the genetic adaptation described?
Multiple lineages can independently become resistant under antibiotic pressure by selecting mutations that increase drug efflux
Ciprofloxacin directly causes bacteria to express new efflux genes that were not present in the genome
Resistance will disappear immediately if ciprofloxacin is stopped because efflux mutations are not heritable
All resistant isolates must have arisen from a single clone that spread between wards
Explanation
This question tests understanding of convergent evolution and selection pressure in antibiotic resistance. When bacteria face strong selective pressure from antibiotics, multiple independent lineages can evolve similar resistance mechanisms through different mutations that achieve the same functional outcome. The passage shows that ciprofloxacin-resistant isolates in Ward A are genetically diverse (not clonal) yet share mutations increasing efflux pump activity. This pattern indicates that ciprofloxacin exposure selects for any mutation that reduces intracellular drug concentration, leading to parallel evolution of resistance. Choice C (single clone spreading) is incorrect because the genetic diversity contradicts clonal expansion. When analyzing resistance patterns, consider whether selective pressure can drive multiple populations to independently evolve similar adaptive solutions.
A lab engineers E. coli to carry a plasmid with an antibiotic resistance gene under a constitutive promoter. When grown without antibiotic, cells gradually lose the plasmid over many generations. When grown with antibiotic, the plasmid is retained. The resistance gene sequence does not change over time. What outcome is most likely given the genetic adaptation described?
Antibiotic exposure selects for cells that keep the plasmid, increasing the fraction of resistant cells in the population
Antibiotic exposure directly mutates the plasmid into the chromosome, making resistance permanent in all cells
Plasmid loss is prevented by activating DNA repair pathways that specifically replicate plasmids faster than chromosomes
Plasmid retention increases without antibiotic because resistance genes always improve growth rate
Explanation
This question tests understanding of selective pressure in maintaining mobile genetic elements. Plasmids often impose a metabolic burden on host cells, causing their gradual loss in the absence of selection. The passage shows that the resistance plasmid is lost without antibiotic but retained with antibiotic present. This occurs because antibiotic exposure creates strong selection for plasmid-bearing cells - only cells maintaining the plasmid survive and reproduce, increasing their frequency in the population. Choice A (improved growth rate) is incorrect because the plasmid is actually lost without selection, indicating it reduces fitness. When analyzing plasmid dynamics, consider the balance between the cost of plasmid maintenance and the selective advantage it provides under specific conditions.
A research team cultures E. coli in broth containing increasing concentrations of rifampin over 5 days. Rifampin targets bacterial RNA polymerase. On day 5, colonies grow on plates containing rifampin at $50,\mu g/mL$. Sequencing of the rifampin target gene from resistant colonies shows a single nucleotide substitution that changes one amino acid in the RNA polymerase binding pocket. Based on this result, which genetic change is most consistent with the resistance observed?
Increased transcription of the wild-type RNA polymerase gene caused by rifampin exposure
Acquisition of a plasmid encoding a rifampin-degrading enzyme via conjugation
Point mutation in the RNA polymerase gene that reduces rifampin binding while preserving polymerase function
Rifampin-induced formation of endospores that survive antibiotic treatment
Explanation
This question tests understanding of chromosomal point mutations as a mechanism of antibiotic resistance. Point mutations are spontaneous changes in DNA sequence that can alter protein function, particularly when they occur in genes encoding drug targets. The passage describes E. coli developing rifampin resistance through a single nucleotide substitution in the RNA polymerase gene, changing one amino acid in the drug-binding pocket. This mutation reduces rifampin binding while preserving the essential function of RNA polymerase, allowing bacterial survival and growth. Choice A (plasmid acquisition) is incorrect because the passage specifically identifies a chromosomal mutation, not horizontal gene transfer. When evaluating resistance mechanisms, look for evidence of genetic changes (sequencing data) and consider whether the change affects drug-target interaction while maintaining essential cellular functions.
A team isolates a plasmid from a multidrug-resistant Enterococcus strain and introduces it into a sensitive strain by electroporation. The transformed strain becomes resistant to vancomycin. When the plasmid is cured (lost) by growth without selection, vancomycin resistance also disappears. Based on these observations, which outcome is most consistent with the system described?
Resistance results from permanent changes in cell wall structure induced by electroporation
Resistance is carried on the plasmid and is lost when the plasmid is no longer maintained
Resistance is caused by reduced antibiotic exposure during growth without selection
Resistance is due to a chromosomal point mutation that persists even after plasmid curing
Explanation
This question tests understanding of plasmid-mediated antibiotic resistance. Plasmids are extrachromosomal genetic elements that can carry resistance genes and replicate independently of the chromosome. The passage demonstrates that vancomycin resistance is gained when the plasmid is introduced and lost when the plasmid is cured, establishing a direct causal relationship between plasmid presence and resistance phenotype. This indicates the resistance gene resides on the plasmid, not the chromosome. Choice A (chromosomal mutation) is incorrect because chromosomal changes would persist after plasmid loss. When evaluating resistance mechanisms, test whether the trait is stable (chromosomal) or can be gained/lost with mobile genetic elements.