Lecture 20, 10/29 (Dr. Maybruck 5); Microbial Drug Resistance

Audio for lecture 20 on October 29th.

• • Slide 1 Chemotherapy for viral infections (Handout from 10/26)
• Selective toxicity is difficult to achieve with viruses
• Antiviral drugs target points in infectious cycle of viruses
• • Preventing virus entrance into cell
• • Preventing viral replication (duplication of DNA), transcription (synthesis of RNA) and translation (synthesis of proteins).
• Viruses can use our own proteins to make their DNA.
• With our drugs we are trying to prevent the life cycle of the virus. Try to keep the virus from entering the cell.
• • Slide 2
• Different drugs involved in inhibiting viral replication
• • Viral thymine kinase → turns precursor guanine into guanine
• • Acyclovir (“false” guanine) – mimics the precursor guanine. Once it is added to the DNA it prevents extra nucleotides from joining to the strands
• • Azidothymidine (AZT) – mimics thymine. Reverse transcriptase grabs AZT nucleotide and binds it to the Adenine.
• • Nevirapine – non nucelotide reverse transcriptase inhibitor. It bonds to the reverse transcriptase and prevents its function.
• • Slide 3 drug resistance
• Methocillin resistant staphylococcus aureus (MRSA) – developed resistance (“acquired resistance”) to Beta-Lactam drugs. Common hospital infection.
• Why do they have this resistance
• • Some have an Intrinsic resistance – ex. organisms that are responsible for creating the antibiotic.
• Acquired resistance can be looked at two ways:
• • →SPONTANEOUS BENEFICIAL MUTATION
• • Gene is a specific sequence of nucleotides that is going to code for a protein that protein then produces a certain trait.
• • Mutation – a change in the specific nucleotide sequence that will be passed on to the next generation
• 3 types of mutations: lethal, neutral and beneficial.
• Lethal mutation ex. Hexokinase – involved in first step of glucolosis. If it were tainted than glycolosis could not happen resulting in death.
• Neutral – a mutation that results in neither beneficial or lethal. Ex eye color
• Beneficial mutation – increasing that populations ability to reproduce and survive.
• • Point mutation – a change in a few nucleotides
• • Natural selection – picking a trait that benefits the population and passing it on
• • Directional selection – an example of natural selection. This is associated with antibiotic resistance. Environmental pressures cause the organism to begin selecting a trait in the population that will be passed on from one generation to the next. Penicillin is an example of an environmental pressure.
• • →HORIZONTAL GENE TRANSFER
• Conjugation
• • Two microorganisms (of different species) will share information (make a copy of the plasmid) by joining up through conjugation
• • Slide 4 specific mechanisms of drug resistance
• Enzymes are made to inactivate drug
• Beta lactamases – example of an enzyme produced by bacteria that will inactivate the effects of penicillin and cephalosporins. This is one way that MRSA functions (it produces beta lactamase)
• • Slide 5 specific mechanisms of drug resistance
• Impermeability of cell to drug
• Gram negative bacteria
• Active transport pump uses energy to pump out the drug
• • Slide 6 specific mechanisms of drug resistance
• Producing an alteration in the target of the drug.
• Erythromycin
• • Prevents movement of mRNA through the ribosome
• Fungi don’t produce binding substrate at all
• Penicillin binding protein (PBP) – a protein that is used by bacteria to build their peptidoglycan cell walls. This protein readily binds to penicillin and is not a builder of the cell wall. MRSA will alter the attaching sight and the penicillin binding protein will continue to build the wall.
• Alteration of metabolic pathway
• • sulfinimide
  
• changes way the dihydroteric acid is formed