| THE CASE OF A STUBBORN MICROBE |
| A patient you were treating for an infected wound last week returns to your clinic, complaining that the infection is worse. You examine the wound and confirm that, indeed, the infection has become worse, even though you had prescribed a high-dose regimen of antibiotics that targeted the bacterial protein synthetic machinery. After questioning the patient to ensure that she was compliant and took the medication, you elect to prescribe rifampicin, a synthetic derivative of the naturally occurring antibiotic, rifamycin. The patient asks you why you think this antibiotic will work. |
| Comment. Antibiotics work by targeting specific functions in the bacterial cell. In the first round of treatment, you used antibiotics that inhibited the bacterial protein synthetic machinery. In some cases, microbes become resistant to a specific type of antibiotic and it is necessary to target other bacterial functions in order to clear up the infection. Rifampicin inhibits the transcriptional machinery of bacteria, inhibiting the β-subunit of bacterial RNA polymerase. Without the ability to make RNA, the bacterial cell will die. |
| Once RNA polymerase has bound to a promoter, it begins the process of selecting the appropriate complementary ribonucleotide and forming phosphodiester bridges between this nucleotide and the nascent chain, in a process called elongation.
Elongation can be a very rapid process, occurring at the rate of 40 nt per second. For elongation to occur, the double-stranded DNA must be continually unwound, so that the template strand is accessible to the RNA polymerase; DNA topoisomerases I and II are enzymes associated with the transcription complex that have the ability to separate DNA strands so that they are accessible as templates for RNA synthesis.
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