Antibacterial and Antiviral Drugs

1. Antibacterial and Antiviral Drugs Larry J. Scheffler Lincoln High School 1

2. Bacteria Definition Replication Shapes Diseases Antibacterials Penicillin Discovery of Synthesis Structure Ways it functions General Antibacterials Problems Possible solutions Antibacterials 2

3. Characteristics of Bacteria • Single celled or non- cellular • Spherical,spiral or rod–shaped organisms • Lack chlorophyll • Reproduce by fission • Important as pathogens and for biochemical properties. 3

4. Infectious Bacteria • Cocci – Sphericial Often cause sore throats and pneumonia • Bacilli – Rod shaped Mycolbacterium cause tuberculosis • Spirochete – Spiral shaped Syphilis, gum infections 4

5. Structure of a Bacterium • Capsule – Protective layer of bacteria. made of proteins, sugars, and lipids • Cell wall – Provides the bacteria with its shape and structure. • Cell membrane – permeable membrane that transfers nutrients and chemicals in and out of the cell. • Cytoplasm – Liquid within the cell which serves to protect cell parts as well as move materials throughout the cell. Contains glycogen, lipids and other nutrients • Ribosomes – synthesizes proteins. • DNA – Single chromosome controls the functions of the cell. • Flagella – A tail-like appendage used for movement. • Pilus – Small hairs whose purpose is to stick to surfaces. Can also be used in reproduction. 5

6. Structure a Bacterium • Bacteria can be either aerobic or anaerobic • Aerobic:-- require oxygen for metabolism. They are more likely to infect surface areas such as the skin and the respiratory tract. • Anaerobic – multiply in oxygen free and in low oxygen surroundings such as the intestines. 6

7. Replication by Binary Fission One cell is split into two separate cells. 7

8. Bacterial Caused Diseases • Anthrax • Cholera • Plague • Q-Fever • Strep Throat • Staph Infections • Tuberculosis 8

9. The Discovery of Penicillin • Penicillin was discovered in 1929 by scientist Alexander Fleming. • He left for vacation with an agar plate covered with the bacteria Staphylococcus aureus. • When he returned he noticed that the fungus, Penicillium, had grown on the plate • The bacteria colony surrounding the fungus had become transparent because the bacterial cells had undergone lysis. 9

10. Development of Penicillin • Several years later Howard Florey and E.B. Chain stumbled across Fleming’s research papers and were intrigued by his findings. • They were convinced that Flemming’s discovery could save a lot of lives, prevent pain, and make it much easier to fight infectious diseases and prevent other infections. • They developed a way to mass produce penicillin making it available to soldiers wounded in world war II. • Florey and Chain were awarded the Nobel Prize in 1945 for their work on penicillin. 10

11. Penicillin Structure Penicillins have a special structure that allows them to interfere with the formation of the cell wall when bacteria reproduce The general structure of penicillin 11

12. How Does it Function? • Penicillin prevents the cross linking of small peptide chains in peptidoglycan, which is the main polymer in bacterial cell walls. • They do not affect bacteria which already exist, rather Penicillin’s affect the synthesis of new bacteria. • The new bacteria grow without the ability to maintain cell rigidity, making them susceptible to osmotic lysis. 12

13. The Action of Penicillins • The amide group in the beta lactam is more reactive due to the strained ring. • The structure of the beta lactam is similar to the structures of cysteine and valine. • The beta lactam binds to the enzyme that synthesizes the cell wall in bacteria, blocking its action. • As a result the bacteria rupture and break and cannot reproduce. Note the similarities in structure to the beta lactam. 13

14. Bacterial Immunity to Penicillin • Antibiotic Resistance – Mutated bacteria which are immune to antibiotics are more likely to survive when excessive antibacterials are used. • Bacteria develop enzymes known as penicillinases that destroy or render penicillin ineffective. • New antibiotics are developed by changing the R group side chain. 14

15. Structure of Penicillin Penicillin is a group of compounds which all contain the same basic ring structure, known as beta-lactam. It is comprised of two amino-acids (valine and cyteine) through a tripeptide intermediate. The third amino acid (the R group) is replaced by another group, which gives different characteristics to differing penicillins. 15

16. Narrow Range and Broad Range Antibiotics • Narrow range antibiotics target specific kinds of bacteria. They are usually more potent. • Broad range antibiotics are effective against a wide range of bacteria. • When doctors diagnose patients suspected of having bacterial infections, they must first take samples of body fluids, and try to determine the precise type of infection. • A broad range antibiotic might be prescribed initially. Once a bacterial infection is properly diagnosed it may be appropriate to switch to a narrow range antibiotic. 16

17. Overuse of Penicillin • Leads to greater immunity of bacteria to penicillin, since the strongest and most resistant strains survive. • Greater doses of penicillin are required to be effective • Danger of developing super bacteria • Kill beneficial bacteria as well as harmful bacteria 17

18. Penicillin Synthesis A sterilized growth medium and an inoculum of strongly growing hyphae is added to stainless steel fermenters. The fermenters stirred continuously and glucose, nitrate and sterile air are periodically added. 18

19. Antibacterial Phages • These can replace antibacterial drugs such as penicillin by utilizing viruses which infect bacterial cells which causes them to lyse, releasing more of the destructive phages. 19

20. Antivirals 20

21. Viruses Definition Replication AIDS AIDS Definition History of AIDS Ways it can spread Treatment Antivirals 21

22. Virus Characteristics • A virus is an infectious agent found in virtually all life forms. • Viruses consist of genetic material, and have a central core either DNA nor RNA • Although they are infectious agents, they differ from bacteria in that they contain no nucleus or cytoplasm. • They do not feed, excrete, or grow • They cannot reproduce outside of a living cell. 22

23. Virus Structure • There are many types of virus with varying shape and structure. • All virus have a central core of either DNA or RNA surrounded by a coat of regularly packed protein units. • No nucleus or cytoplasm like bacteria. Diagram of an AIDS Virus 23

24. Virus Replication • The replication of viruses can only occur if the virus has attached and penetrated the living host cell. • It injects it’s DNA or RNA into the host cell’s cytoplasm. • It takes over the replication mechanism of the host cell. • This causes the cell to die or to be altered, which results in the symptoms of a viral infection. • The host cell produces new viral DNA or RNA cells which are then released to affect other healthy cells. • A virus that contains RNA rather than DNA is called a retrovirus. 24

25. Virus Replication The virus uses the cell mechanism to replicate itself 25

26. AIDS a Viral Transmitted Disease • A 10-year study completed in 2005 found a strain of Simian Immunodeficiency Virus (SIV) in a number of chimpanzee colonies in south-eastern Cameroon that was a viral ancestor of the HIV-1 that causes AIDS in humans.     • In 1981 AIDS was first identified within homosexual men 26

27. AIDS in the US • 940,000 cases of AIDS were reported in the United States from 1981 through 2004. • In 2004, about 39,000 new cases of HIV infection were reported. • Currently, there are approximately 1.1 million people in the United States who are infected with the human immunodeficiency virus. 27

28. History of AIDS in Africa • Wide spread in Africa. • Lack of access to education. • Reticence of some leaders to recognize the problem. • Lack of access to treatment. 28

29. AIDS Definition AIDS ( Acquired Immune Deficiency Syndrome) is caused by a retrovirus that contains RNA rather then DNA. This specific virus invades particular cells, that are within the immune system making the body unable to fight off infections. 29

30. AIDS Definition The human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), principally attacks T-4 lymphocytes, a vital part of the human immune system. • As a result, the ability of the body to resist opportunistic viral, bacterial, fungal, protozoal, and other infections is greatly weakened. 30

31. 3 Ways AIDS can be spread Scientists have identified three ways that HIV infections spread: • Sexual intercourse with an infected person, • Contact with contaminated blood, • Transmission from an infected mother to her child before or during birth or through breastfeeding. 31

32. AIDS Diagnosis and Treatment • While no medical treatment cures AIDS, there are many drugs that have recently been developed to eradicate the HIV virus. • Full blown symptoms of AIDS may not appear for more then 10 years. • It usually takes 2-3 months after the initial infection for a person to test positive for HIV 32

33. AIDS Diagnosis and Treatment • While no medical treatment cures AIDS, there are many drugs that have recently been developed to eradicate the HIV virus. • Although full blown symptoms of AIDS may not appear for more then 10 years. • It usually takes 2-3 months after the initial infection for a person to test positive for HIV • During this time frame a person inflected with HIV can easily spread the virus without realizing it. 33

34. Antiviral Drugs • Common viral infections such as the influenza, mumps, or chicken pox are usually overcome by the body’s immune system. • Vaccines are often used to build up immunity before a viral inflection occurs. • Medications for viral diseases are used to: • relieve associated pain, • reduce fever, or • counteract secondary inflections • Rapid replication of viruses makes it difficult to develop effective antiviral drugs. The viruses are often very high even before the first symptoms appear. 34

35. Antiviral Drugs • Only a few effective antiviral drugs have been developed. • Antiviral drugs work by • Altering the cell’s genetic material so that the virus cannot use it to multiply, i.e. acyclovir • Preventing new virus formed from leaving the cell, i.e. amatadine • Viruses mutate frequently leaving the antiviral drug ineffective 35

36. Antiviral Drugs - Acyclovir Acyclovir is an antiviral drug used to treat Herpes Simplex Acyclovir has a structure similar to deoxyguanosine, one of the building blocks of DNA. It tricks the viral enzyme DNA polymerase into incorporating it into its DNA instead of guanine making it impossible to replicate. 36

37. Antiviral Drugs - AZT AZT was the first antiviral drug used to effectively treat HIV-AIDS . AZT combines with the enzyme that the HIV virus uses to build DNA from RNA and clogs up its active site. It acts as a reverse transcriptase inhibitor. Since only Retro-Viruses, such as HIV, use this enzyme, AZT does not affect normal cells. Unfortunately it causes anaemia 37

38. Other HIV Antiviral Drugs More recently ddI and ddC have been developed for HIV treatment. While antiviral drugs show promise in preventing AIDS in people who are HIV positive, these drugs are still very expensive and not available to many people who are HIV positive, 38

39. Other Antiviral Drugs Recently, a series of nucleoside have been developed that appear to be effective against herpes virus. .. 39