질병과 미생물

1. 질병과 미생물

2. 약 주는 미생물 항생물질 (antibiotics) 합성항생제 (syntheticantimicrobial drugs)

3. Antibiotics are naturally produced antimicrobial agents • Less than 1% of known antibiotics are clinically useful • Can be modified to enhance efficacy (semisynthetic) • The susceptibility of microbes to different antibiotics varies greatly • Gram-positive and gram-negative bacteria vary in their sensitivity to antibiotics such as penicillin • Broad-spectrum antibiotics are effective against both groups of bacteria

4. Spectrum of activity of natural and synthetic antimicrobial drugs

5. Mode of action of some major antibacterial antibiotic agents

6. Penicillin • Penicillin: discovered by Alexander Fleming • Produced from fungi, PenicilliumnotatumandPenicilliumchrysogenum • Primarily effective against gram-positive bacteria • Some synthetic forms are effective against some gram-negative bacteria • Target cell wall synthesis

7. Penicillins

8. Antibiotics from bacteria • Many antibiotics effective against Bacteria are also produced by Bacteria • Streptomycin, tetracyclines, erythromycin, kanamycin, neomycin, etc.

9. Tetracycline

10. Antiviral drugs • Interferons are small proteins that prevent viral multiplication by stimulating antiviral proteins in uninfected cells • Most synthetic antiviral drugs also target host structures, resulting in toxicity • A few antivirals specifically target viruses

11. Antifungal drugs • Fungi pose special problems for chemotheraphy because they are eukaryotic • Much of the cellular machinery is the same as that of animals and humans • As a result many antifungals are topical • There are a few drugs that target unique metabolic processes • Antifungal-resistant fungi are emerging

12. Action of some antifungal chemotherapeutic agents

13. Antimicrobial drug resistance • Antimicrobial drug resistance • The acquired ability of a microbe to resist the effects of a chemotherapeutic agent to which it is normally sensitive • At least six reasons that microbes are naturally resistant to certain antibiotics • Organism lacks structure the antibiotic inhibits • Organism is impermeable to antibiotic • Organism can inactivate the antibiotic • Organism may modify the target of the antibiotic • Organism may develop a resistant biochemical pathway • Organism may be able to pump out the antibiotic (efflux)

14. Antimicrobial drug resistance • Most drug-resistant bacteria isolated from patients contain drug-resistance genes located on R plasmids • Evidence indicates that R plasmids predate the antibiotic era • The use of antibiotics in medicine, veterinary, and agriculture select for the spread of R plasmids • Many examples of overuse of antibiotics • Used far more often than necessary (i.e., antibiotics used in agriculture as supplements to animal feed)

15. Patterns of Drug Resistance in Pathogens

16. Patterns of Drug Resistance in Pathogens

17. Patterns of Drug Resistance in Pathogens

18. Antimicrobial drug resistance • Almost all pathogenic microbes have acquired resistance to some chemotherapeutic agents • A few pathogens have developed resistance to all known antimicrobial agents • Methicillin-resistant S. aureus • Resistance can be minimized by using antibiotics correctly and only when needed • Resistance to a certain antibiotic can be lost if antibiotic is not used for several years

19. The Appearance of Antimicrobial Drug Resistance

20. The search for new antimicrobial drugs • Long-term solution to antimicrobial resistance relies on the development of new antimicrobial compounds • Modification of current antimicrobial compounds is often productive • Automated chemistry methods has sped up drug discovery • 7,000,000 compounds must be screened to find a single useful clinical drug

21. The search for new antimicrobial drugs • Computers can now be used to design molecules to interact with specific microbial structures • Most successful example is saquinavir • Binds to active site of HIV protease • New methods of screening natural products are being used • i.e., the discovery of platensimycin • Combinations of drugs can be used (I.e., ampicillin and sulbactam) • Bacteriophage therapy

22. Vancomycin

23. Computer-generated anti-HIV drugs