Chapter 9
Microbial Genetics
I.
Introduction
An easily treatable infection with a common bacterial species (Staphylococcus aureus)
becomes much more difficult to treat as it gains a new trait; namely the ability to resist
the effects of the drug vancomycin. This ability is genetically controlled and analysis of
the case will show that it was most likely acquired from the vancomycin-resistant strain
of Enterococcus faecalis isolated from the patient’s chronic foot ulcer.
II.
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Facts of the Case
Vancomycin-resistant Staphylococcus aureus is isolated from an individual. This
is the first time an S. aureus strain with this particular trait has been seen.
During a prior surgery, infection with methicillin-resistant Staphylococcus aureus
was treated with rifampin and, more importantly, vancomycin.
The patient has several underlying health problems, which made him an attractive
target for VRE infection (diabetic, chronic renal failure necessitating dialysis,
chronic foot ulcers, and poor circulation). In fact, one week after the MRSA
infection was treated, Vancomycin-resistant Enterococcus faecalis was cultured
from the foot ulcer.
Genetic analysis of the VRSA isolate revealed that it contained the most common
vancomycin resistance gene (vanA) as well as the mecA gene which provides
resistance to methacillin and oxacillin.
Student questions:
1. What is the difference between genotype and phenotype? What two
phenotypes are of particular interest in this case?
2. What biological molecules directly control genotype and phenotype? Briefly
provide their functions and explain the flow of information between them.
3. How does a cell “know” when to develop a useful mutation like vancomycin
resistance?
4. When the patient in the case study was treated with vancomycin, what was
the effect on S. aureus cells that were not resistant to the drug? What about
those cells that were resistant?
5. Methicillin acts by binding to a specific protein in the cell wall known as
PBP2a (Penicillin binding protein 2a), and inhibiting cell wall synthesis.
Methicillin resistance occurs when an altered form of this protein is
produced by a bacterial cell, and methicillin can no longer bind. Briefly
discuss how a change in the DNA of a bacterial cell could lead to production
of an altered PBP2a protein. Do all changes in the DNA of an organism lead
to new functions? What other outcomes can you postulate?
6. Do all mutations result in the same degree of change to the final protein
product?
7. Are changes in transcription and translation mistakes as crucial as those in
replication?
8. The VRSA isolated from the catheter exit site of the patient contained a
previously identified vanA mutation commonly seen in many species of
Enterococcus, making it unlikely that a new mutational event conferred
vancomycin resistance on the already methicillin resistant Staph aureus
isolate. Given this fact, how else could the S. aureus isolate have obtained the
new phenotype? Start by establishing a timeline placing the major events of
the case in chronological order.
9. Why would this particular patient be at increased risk for infection with
VRSA?