Chapter 1: A Brief History of Microbiology

1. Chapter 1: A Brief History of Microbiology

2. Microbiology: The study of microorganisms. Microorganisms: Small living organisms that generally can not be seen with the naked eye. Include: • Bacteria • Fungi (yeasts and molds) • Protozoa • Algae • Multicellular parasites Also include nonliving infectious agents: • Viruses • Prions

3. Microbes are Essential for Life on Earth: Have many important and beneficial biological functions: • Photosynthesis: Algae and some bacteria capture energy from sunlight and convert it to food, forming the basis of the food chain. • Decomposers: Many microbes break down dead and decaying matter and recycle nutrients that can be used by other organisms. • Nitrogen Fixation: Some bacteria can take nitrogen from air and incorporate it into soil.

4. Important and beneficial biological functions of Microbes: • Digestion: Animals have microorganisms in their digestive tract, that are essential for digestion, vitamin synthesis, and overall health. • Cellulose digestion (termites, cows, rabbits, etc.) • Vitamin K and B synthesis in humans • Prevent the overgrowth of pathogenic bacteria and yeast • Medicine: Many antibiotics and other drugs are naturally synthesized by microbes. • Penicillin is made by a mold

5. Penicillin is Produced by a Mold

6. Important and beneficial biological functions of Microbes: • Food Industry: Many important foods and beverages are made with microbes: • Alcoholic beverages (Wine, beer, rum, whiskey) • Bread • Vinegar • Soy sauce • Cheese • Pickles, olives, sauerkraut • Yogurt • Buttermilk • Sour cream • Coffee • Chocolate • Hams, sausages

7. Important and beneficial biological functions of Microbes: • Genetic Engineering: Recent advances in gene splicing allow us to design recombinant microbes that produce important products: • Human growth hormone (Dwarfism) • Insulin (Diabetes) • Blood clotting factor (Hemophilia) • Recombinant vaccines • Hepatitis A and B vaccines • Human hemoglobin (Emergency blood substitute) • Taxol (Breast and ovarian cancer) • Erythropoietin (Anemia) • Monoclonal antibodies (Disease diagnosis and prevention).

8. Important and beneficial biological functions of Microbes: • Medical Research: Microbes are well suited for biological and medical research for several reasons: • Relatively simple and small structures, easy to study. • Genetic material is easily manipulated. • Can grow a large number of cells very quickly and at low cost. • Short generation times make them very useful to study genetic changes.

9. Microbes and Disease:Most microbes are either beneficial or harmless to humans. • Less than 1% of microbes cause disease. • In 1962, the surgeon general of the United States stated: “The war against infectious diseases has been won”. • Today it is clear that this was overly optimistic: • Emerging diseases: New diseases like AIDS, hantavirus, Ebola fever, Lyme disease, Hepatitis C, and others that did not exist a few years ago. • Antibiotic and Drug Resistance: Many old diseases are becoming resistant to traditional therapies: Tuberculosis, gonorrhea, malaria, etc. • Today infectious diseases cause 50% of the 52 million worldwide deaths per year.

10. Infectious Diseases Causing Most Deaths Worldwide in 2000 DiseaseCauseDeaths/year Acute Respiratory*Bacterial or viral 4,400,000 Diarrheal diseases Bacterial or viral 3,200,000 Tuberculosis Bacterial 3,100,000 Malaria Protozoan 3,100,000 Hepatitis B Viral 2,000,000 Measles Viral 1,500,000 AIDS Viral 1,000,000 Neonatal Tetanus Bacterial 600,000 *: Pneumonia, bronchitis, influenza, etc.

11. Neonatal tetanus kills over 600,000 infants every year. Source: Tropical Medicine and Parasitology, 1997.

12. Microbes and Disease in Human History • Bubonic Plague (Black death): Several devastating epidemics throughout history. • High mortality: Up to 80% of those infected die. • 1347-1351: Over 75 million died in Europe, Asia, and Africa. • Over 25% of population of Europe died. • Cause was unknown for over 500 years, leading to superstition, persecution, and hysteria. • Bacterial disease transmitted by rat fleas. • Rare today but still occurs: • 10-15 cases/year in U.S. • Last epidemic occurred in India in 1994.

13. Left: Swollen lymph nodes in bubonic plague infection. Right: Infected flea bite with eschar and carbuncle. Source: Tropical Medicine and Parasitology, 1997.

14. Worldwide Distribution of Plague ++: Frequent transmission +/-: Infrequent transmission. Source: Tropical Medicine and Parasitology, 1997.

15. Smallpox:One of deadliest human infectious diseases throughout history. • Caused by smallpox virus. • First known case in 1175 B.C.: Egyptian pharaoh Ramses V died from smallpox. • Several hundred million deaths through history. • Up to 90% of Native American population was killedby smallpox and other diseases (measles and plague) introduced during European conquests. • Native population of Central and South America dropped from 130 million to about 1.6 million over several decades. • Smallpox was used as abiological weaponby British colonists in North America. • 600,000 deaths/year in Europe from 1500-1700.

16. Smallpox infection in a small child. Disease was eradicated worldwide by immunization in 1977. Source: Microbiology Perspectives, 1999.

17. Smallpox (Continued) • 75% of survivors were severely scarred and/or blinded. • An effective vaccine was developed in 1870s by Edward Jenner, using a related virus (cowpox). • Smallpox was the first and only viral disease to be completely eradicated (1977). • Worldwide immunization campaign in 1960s. • Only infects humans.

18. Tuberculosis (TB): Caused by a bacterium that mainly infects lungs but may spread to other parts of body. • Leading killer of world’s infectious diseases: • 3 million die worldwide every year. • Over 1 million killed in U.S. between 1930-49. • One out of three people infected worldwide. • In U.S. 10 million people are presently infected, but only 5% will develop active disease. • Most healthy individuals can contain infection. • Treatment: Antibiotics for up to one year or longer. • After introduction of antibiotics, TB declined from 1950s to 80s, and then started to increase again. • Low patient compliance with treatment has caused antibiotic resistant TB. • AIDS epidemic has caused an increase in cases.

19. Tuberculosis is leading killer among infectious diseases worldwide. Patient with lymph node necrosis. Photo by Dr. I. Small

20. Childbirth Fever: Commonnosocomial (hospital acquired) infection. • Bacterial infection of the uterus as a result of childbirth or abortion. • Transmitted by hands and instruments of physicians and midwives. • Extremely common before the 1900s. • About 1 in 17 women who gave birth would become infected (fever, chills, delirium, and death). • Cause was unknown. • Austrian doctor Semmelweiss showed that washing hands and instruments with a disinfectant solution greatly reduced cases. • Today common in women who have illegal abortions, especially in third world countries.

21. AIDS: Acquired Immune Deficiency Syndrome. • First cases reported in 1981 at UCLA. • Cause: HumanImmunodeficiencyVirus (HIV) • Transmitted by sexual contact, blood transfusions, mother-to-child, and infected needles. • Destroys an individual’s immune system, making them susceptible to many infectious diseases and cancer. • Number of cases has grown rapidly during the last two decades. As of 2004: • Over 1’000,000 individuals with AIDS in the U.S. • Over 500,000 US AIDS patients have died • Over 40 million deaths worldwide.

22. African AIDS patient with slim disease Source: Tropical Medicine and Parasitology, 1997

23. Endemic Kaposi’s Sarcoma, nodular form in an AIDS patient. Source: AIDS, 1997.

24. Extensive symmetric tumor lesions of Kaposis’s sarcoma in an AIDS patient. Source: AIDS, 1997

25. Oral candidiasis (yeast infection) in an AIDS patient Source: Atlas of Clinical Oral Pathology, 1999

26. History of Microbiology Early Studies Before 17th century, study of microbiology was hampered by the lack of appropriate tools to observe microbes. • Robert Hooke: In 1665 built a compound light microscope and used it to observe thin slices of cork. Coined the word cell. • Anton van Leeuwenhoeck: In 1673 was the first person to observe live microorganisms which he called “animalcules” (bacteria, protozoa), using single-lens microscopes that he designed.

27. History of Microbiology Spontaneous Generation vs Biogenesis • Before 1860s many scientists believed in Spontaneous generation, i.e.: That living organisms could arise spontaneously from nonliving matter: • Mice come from rags in a basket. • Maggots come from rotting meat. • Ants come from honey. • Microbes come from spoiled broth.

28. History of Microbiology Spontaneous Generation vs Biogenesis • Theory of Biogenesis: Belief that living cells can only arise from other living cells. • Francesco Redi: In 1668 proved that maggots do not arise spontaneously from decaying meat. • Lazaro Spallanzani: In 1765 found that nutrient broth that had been heated in a sealed flask would not become contaminated with microbes. • Some proponents of spontaneous generation argued that boiling had destroyed the “life force” of air in flask. • Others argued that microbes were different from other life forms.

29. History of Microbiology Spontaneous Generation vs Biogenesis Debate was finally settled by Pasteur. • Louis Pasteur: In 1861 finally disproved spontaneous generation when he demonstrated that microorganisms in the environment were responsible for microbial growth in nutrient broth. • Designed swan neck flasks that allowed air in, but trapped microbes in neck. • Developed aseptic technique: Practices that prevent contamination by unwanted microorganisms.

30. History of Microbiology Golden Age: 1857-1914 Rapid advances led to the development of microbiology as a science. Pasteur’s Contributions to Microbiology: • Fermentation: Pasteur found that yeasts were responsible for converting sugar into alcohol in the absence of air. • Souring and spoilage were caused by bacterial contamination of beverages.

31. History of Microbiology Golden Age: 1857-1914 Pasteur’s Contributions: • Pasteurization: Developed a process in which liquids are heated (at 65oC) to kill most bacteria responsible for spoilage. • Disease Causes: Identified three different microbes that caused silkworm diseases. • Vaccine: Developed a vaccine for rabies from dried spinal cords of infected rabbits. • Directed Pasteur Institute until his death in 1895.

32. History of Microbiology Golden Age: 1857-1914 Germ Theory of Disease: Belief that microbes cause diseases. Before, most people believed diseases were caused by divine punishment, poisonous vapors, curses, witchcraft, etc. • Agostino Bassi (1835): Found that a fungus was responsible for a silkworm disease. • Ignaz Semmelweis (1840s): Demonstrated that childbirth fever was transmitted from one patient to another, by physicians who didn’t disinfect their hands. He was ostracized by colleagues.

33. History of Microbiology Golden Age: 1857-1914 Germ Theory of Disease: • Joseph Lister (1860): Used disinfectant to treat surgical wounds, greatly reducing infection rates. Considered the father of antiseptic surgery. • Robert Koch (1876): First person to conclusively prove that a specific bacterium caused a disease. • Germ Theory: One microbe causes one specific disease. • Proved that Bacillus anthracis causes anthrax in cattle. • Later identified bacterium that causes tuberculosis.

34. History of Microbiology Modern Microbiology: After 1914 Chemotherapy: Treatment of a disease by using a chemical substance. Chemical must be more poisonous to microbe than host. • Quinine: First known chemical to treat a disease (malaria). Used by Spanish conquistadors. • Synthetic Drugs: Made in the laboratory. • Antibiotics: Produced naturally by fungi and bacteria.

35. History of Microbiology Modern Microbiology: After 1914 • Paul Ehrlich (1910): Search for “magic bullet”. • Discovered salvarsan, an arsenic derivative, was effective against syphilis. • Alexander Fleming (1928): Discovered that penicillin produced by the mold Penicillium notatum was able to prevent microbial growth. • Penicillin was not mass produced until the 1940s. • Rene Dubos (1939): Discovered two antibiotics (gramidin and tyrocidine) produced by bacterium (Bacillus brevis).

36. History of Microbiology Modern Microbiology: After 1914 Problems with Chemotherapy: • Toxicity • Drug resistant microbes

37. Diversity of Microorganisms I. Bacteria (Sing. Bacterium) • Small, single-celled (unicellular) organisms. • Procaryotes: “Before nucleus”. Lack the following structures: • Nuclear membrane around DNA • Membrane bound organelles • Mitochondria • Chloroplasts • Golgi apparatus • Endoplasmic reticulum • Lysosomes

38. Kingdom Prokaryotae: Bacteria lack nucleus and membrane bound organelles

39. Diversity of Microorganisms I. Bacteria (Sing. Bacterium) • Include two groups: • Eubacteria: Peptidoglycan cell walls. • Archaebacteria: Lack peptidoglycan cell walls. • Shapes: Several forms: • Bacilli: Rod like. (Sing. Bacillus) • Cocci: Spherical. (Sing. Coccus) • Spiral: Corkscrew or curved • Square • Star shaped

40. Diversity of Microorganisms I. Bacteria (Sing. Bacterium) • Divide by binary fission (not mitosis). • Source of nutrients varies: • Heterotrophs: Consume organic chemicals. • Autotrophs: Make their own food. Include photosynthetic bacteria. • Motility: Many can “swim” by using moving appendages: • Cilia: Small hair like structures • Flagella: Large whip like structures. • Distinguish between motility and Brownianmotion.

41. Diversity of Microorganisms II. Fungi (Sing. Fungus) • Eucaryotes: “True nucleus” • DNA is surrounded by nuclear membrane. • Cells have membrane bound organelles: Mitochondria, endoplasmic reticulum, etc. • Cells are larger than those of procaryotes. • May be unicellular or multicellular: • Unicellular: Yeasts • Multicellular: Molds, mushrooms • Do not carry out photosynthesis. • Must absorb organic nutrients from their environment.

42. Diversity of Microorganisms II. Fungi (Sing. Fungus) • Source of nutrients varies: • Saprotrophs: Decomposers that feed on dead and decaying matter. Most fungi are decomposers. • Parasites: Obtain nourishment by parasitizing live animals and plants. • Cell wall made of chitin. • May reproduce sexually or asexually.

43. Diversity of Microorganisms III. Protozoa (Sing. Protozoan) • Eucaryotes: “True nucleus” • DNA is surrounded by nuclear membrane. • Cells have membrane bound organelles and are larger than those of procaryotes. • Unicellular • Kingdom Protista • Sexual or asexual reproduction • Classified based on locomotion: • Pseudopods: “False feet”. Cytoplasmic extensions. • Example: Amoeba

44. Protozoa Belong to Kingdom Protista: Eucaryotic Unicellular or Simple Multicellular Organisms

45. Diversity of Microorganisms III. Protozoa (Sing. Protozoan) • Classified based on locomotion: • Flagella: Long whip like appendages. • Example: Trichomonasvaginalis, causes trichominiasis, a sexually transmitted disease. • Cilia: Small hair like appendages • Nonmotile: Do not move in their mature forms. • Example: Plasmodium spp., causative agent of malaria.

46. Diversity of Microorganisms IV. Algae (Sing. Alga) • Eucaryotes: “True nucleus” • Photosynthetic: Important part of food chain because produce oxygen and carbohydrates used by animals. • Unicellular or multicellular • Kingdom Protista • Sexual or asexual reproduction • Cell walls composed of cellulose • Found in aquatic environments (oceans, lakes, rivers), soil, and in association with plants.

47. Diversity of Microorganisms V. Viruses • Acellular infectious agents, not considered living because they lack cells. • Obligate intracellular parasites: Viruses can only reproduce by using the cellular machinery of other organisms. • Simple structure: • Protein coat (capsid) with either DNA or RNA, but not both. • May also have a lipid envelope.

48. Comparison of Cells and Viruses

49. Diversity of Microorganisms VI. Multicellular Animal Parasites • Eucaryotes: “True nucleus” • Multicellular animals, usually are visible to the naked eye. • Microscopic during some stages of life cycle. • Spend part or all of their lives inside an animal host. • Helminths include: • Flatworms (Platyhelminths): E.g. Tapeworm • Roundworms (Nematodes): E.g. Ascaris, pinworm.