1. Prokaryotic Diversity and Molecular Genetics Biol 103 Diversity of Life

2. Scott Samuels Office: Science Complex 207 Phone: 243-6145 Email: samuels@selway.umt.edusamuels@selway.umt.edu Office hours: Monday, Tuesday, Wednesday 2:10 pm–3:00 pm

3. My research interests: DNA supercoiling DNA supercoiling (and higher-order structure) DNA topoisomerases (gyrase)DNA topoisomerases (gyrase) Regulation of transcription Regulation of transcription Mechanism of replication Mechanism of replication (linear DNA in bacteria) Antibiotic resistance Antibiotic resistance My favorite system: Borrelia burgdorferi -causative agent of Lyme disease

4. Theme: Prokaryotic Diversity and Molecular Genetics 1. Antibiotic resistance 2. Prokaryotic diversity 3. DNA structure and function 4. DNA replication 5. Bacterial genetics 6. Gene expression 7. The lac operon 8. Seminar: Lyme disease gene regulation

5. Antibiotic Resistance I. Antibiotics A. Definition B. Mechanisms of action (targets) C. Disease treatment II. Resistance

6. Reading (1) The challenge of antibiotic resistance, Levy, Scientific American, March 1998 (Web)Web

7. What is an antibiotic?

8. Antibiotics Organic substances that are either toxic or growth-inhibitory for organisms Infectious disease therapy depends on selective toxicity Target is a structure (or function) only found in specific organism Focus on antibiotics that target bacteria

9. Targets of antibacterial agents Penicillins, bacitracin, and vancomycin Aminogylcosides, tetracyclines, and erythromycin Rifamycins Fluoroquinolones and coumarins Cell wall synthesis Protein synthesis (ribosomes) RNA synthesis DNA synthesis (gyrase)

10. Treatment of bacterial diseases Strep throat (Streptococcus pyogenes) Pneumonia/ear infections (S. pneumoniae) Gonorrhea (Neisseria gonorrhoeae) Lyme disease (Borrelia burgdorferi) RMSF (Rickettsia rickettsii) Tuberculosis (Mycobacterium tuberculosis) …and many others….

11. Antibiotic Resistance I. Antibiotics II. Resistance A. Mechanisms B. Acquisition/Evolution C. Factors D. Preventative actions

12. How do disease-causing bacteria become resistant to antibiotics? What mechanisms do bacteria use to become resistant to antibiotics?

13. Mechanisms of antibiotic resistance Keep antibiotic out of cell Pump antibiotic out of cell Inactivate antibiotic –destroy –modify Change target

14. How do bacteria acquire these mechanisms of antibiotic resistance?

15. Acquiring resistance Obtain genetic element from others Plasmid/gene uptake (transformation) Virus (transduction) Sex (conjugation) Mutate (change DNA sequence) Overproduction of target Alteration of target Loss of target

16. Evolution of genetic elements that encode resistance Found in a remote community in Borneo that had never been exposed to antibiotics Survival mechanism in presence of antibiotics produced by other organisms in soil or bowel (Davis et al., 1970)

17. Factors that contribute to antibiotic resistance Overuse of antibiotics –meat and dairy production Inappropriate use of antibiotics –no effect on viral diseases Incomplete use of antibiotics –not finishing prescription

18. Antibiotic resistance as a public health problem Methicillin-resistant Staphylococcus aureus Vancomycin-resistant enterococci Penicillin-resistant pneumococci Drug-resistant gonorrhea Multidrug-resistant tuberculosis

19. Antibiotic residues in milk The existing antibiotic testing program cannot guarantee that illegal residues are not present in the milk supply (GAO, 1990, 1992) Even FDA “safe levels” (from 10 to 150 parts per billion) of antibiotic residues can select for antibiotic resistance in S. aureus (Brady et al., 1993)

20. Actions you can take to limit the development of antibiotic resistance Do not demand antibiotics from your physician. When given antibiotics, take them exactly as prescribed and complete the full course of treatment; do not hoard pills for later use or share leftover antibiotics.

21. Your mother was right:

22. Wash fruits and vegetables thoroughly; avoid raw eggs and undercooked meat, especially in ground form. (The majority of food items that cause diseases are raw or undercooked foods of animal origin such as meat, milk, eggs, cheese, fish or shellfish.) Use soaps and other products with antibacterial chemicals only when protecting a sick person whose defenses are weakened. Alliance for the Prudent Use of Antibiotics

23. Summary Antibiotics are “miracle drugs” Antibiotic resistance: “the new apocalypse” Wash hands and use antibiotics prudently

24. Reading (2) Chapter 27

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