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Chapter 1: A Brief History of Microbiology

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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 Table 1.1 Some Industrial Uses of Microbes

9 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.

10 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 ~25% of the 53 million worldwide deaths per year.

11 Leading Causes of Death Worldwide 2000 and 2011*
Source: World Health Org. 2013

12 Top Infectious Diseases Causing Deaths Worldwide in 2010**
Disease Cause Deaths/year Acute Lower Respiratory* Bacterial/viral/other 2,800,000 Diarrheal diseases Bacterial/viral/other 1,500,000 AIDS/HIV Viral 1,500,000 Tuberculosis Bacterial 1,200,000 Malaria Protozoan 1,100,000 Neonatal infection/sepsis Bacterial/viral/other 514,000 Meningitis Bacterial or viral ,000 Hepatitis Viral (A/B/C/D) ,000 Typhoid/Paratyph. fever Bacterial ,000 Measles Viral ,000 Encephalitis Bacterial/viral/other 120,000 Syphilis Bacterial ,000 Whooping cough Bacterial ,000 Tetanus Bacterial ,000 ** Source: Lozano et al. Lancet 2012: 380: *Pneumonia, bronchitis, influenza, etc.

13 Neonatal tetanus kills thousands of infants every year.
Source: Tropical Medicine and Parasitology, 1997.

14 Microbes and Disease in Human History
Bubonic Plague (Black death): Several devastating epidemics throughout history. High mortality: Up to 80% of those infected die. : 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.

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

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

17 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 killed by 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 a biological weapon by British colonists in North America. 600,000 deaths/year in Europe from

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

19 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.

20 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 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.

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

22 Childbirth Fever: Common nosocomial (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.

23 AIDS: Acquired Immune Deficiency Syndrome.
First cases reported in 1981 at UCLA. Cause: Human Immunodeficiency Virus (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 2010: Over 1’200,000 individuals live with AIDS in the U.S. Over 630,000 US AIDS patients have died Over 40 million deaths worldwide.

24 AIDS patients with wasting and Kaposi’s Sarcoma
Source: Tropical Medicine and Parasitology, 1997 and AIDS, 199

25 New HIV Infections in the United States, 2010
n = 49,273, CDC

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 Antoni van Leeuwenhoek

28 Spontaneous Generation vs Biogenesis
Early 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.

29 Spontaneous Generation vs Biogenesis
Early 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.

30 Francesco Redi’s Experiments

31 Spontaneous Generation versus 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.

32 Pasteur’s experiments with “swan-necked” flasks
Steam escapes from open end of flask. Dust from air settles in bend. Air moves in and out of flask. Months Infusion is heated. Infusion sits; no microbes appear. Infusion remains sterile indefinitely.

33 History of Microbiology
Golden Age: 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.

34 Golden Age of Microbiology
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.

35 Golden Age of Microbiology
Germ Theory of Disease: Belief that microbes cause diseases. Before Pasteur, most people believed diseases were caused by divine punishment, toxic vapors, curses, evil spirits, 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.

36 Golden Age of Microbiology
Germ Theory of Disease: Microbes cause specific diseases. Joseph Lister (1860): Used disinfectant to treat surgical wounds, greatly reducing infection rates. Considered the founder of antiseptic surgery. Florence Nightingale ( ): English nurse who introduced cleanliness and other aseptic techniques into nursing practice. Founded the first nursing school.

37 Golden Age of Microbiology
Robert Koch (1876): First person to conclusively prove that a specific bacterium caused a disease. Koch Advanced Germ Theory: One microbe causes one specific disease. Koch studied the etiology of infectious diseases and proved that: Bacillus anthracis causes anthrax in cattle. Mycobacterium tuberculosis causes tuberculosis.

38 Koch Isolated and Studied Bacterial Pathogens
Bacterium 6 Bacterium 7 Bacterium 5 Bacterium 8 Bacterium 4 Bacterium 9 Bacterium 3 Bacterium 10 Bacterium 2 Bacterium 11 Bacterium 1 Bacterium 12

39 Koch’s Contributions to Microbiology
Developed Koch’s postulates: a series of steps to identify bacterial pathogens Simple staining techniques First photomicrograph of bacteria Techniques for estimating bacterial counts Use of steam to sterilize growth media Use of Petri dishes to grow bacteria Aseptic techniques to transfer bacteria Bacteria as distinct species

40

41 Gram’s Stain In 1884 Danish scientist Hans Christian Gram developed more important staining technique Involves the applications of a series of dyes The Gram procedure is used to separate into two groups: Some microbes are left purple, now labeled Gram-positive Other microbes are left pink, now labeled Gram-negative

42 Results of Gram staining
Gram-positive Gram-negative Results of Gram staining

43 History of Microbiology Modern Microbiology: 20th Century
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.

44 History of Microbiology Modern Microbiology: 20th Century
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).

45 Modern Microbiology Problems with Antimicrobial Chemotherapy:
Side Effects Toxicity: Damage to liver, kidney, bone marrow, teeth, fetus, etc. Dysbiosis: Destruction of beneficial microbes can cause diarrhea, nausea, cramps, yeast infections, etc. Allergic reactions: Anaphylactic reactions to penicillin, rashes, etc. Drug resistant microbes: Multi-Drug Resistant Strains Staphylococcus aureus (MRSA) Tuberculosis (XDR TB) Malaria

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

47 Kingdom Prokaryotae: Bacteria lack nucleus and membrane bound organelles

48 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

49 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 called flagella: Large whip-like structures. Distinguish between motility and Brownian motion.

50 Diversity of Microorganisms
II. Fungi (Sing. Fungus) Eukaryotes: “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. Absorb organic nutrients from their environment.

51 Fungi Include Molds and Yeasts

52 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.

53 Diversity of Microorganisms
III. Protozoa (Sing. Protozoan) Eukaryotes: “True nucleus” DNA is surrounded by nuclear membrane. Cells have membrane bound organelles and are larger than those of prokaryotes. Unicellular Sexual or asexual reproduction Classified based on locomotion: Pseudopods: “False feet” (e.g. Amoeba) Flagella: Long appendages (e.g. Trichomonas vaginalis) Cilia: Small hair-like appendages (e.g. Paramecium) Nonmotile: Do not move in their mature forms (e.g. Plasmodium spp., causative agent of malaria)

54 Protozoa: Eukaryotic Unicellular Organisms

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

56 Algae: Simple Photosynthetic Commonly Aquatic Organisms

57 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.

58 Comparison of Cells and Viruses

59 Viruses Infecting a Bacterium
Viruses assembling inside cell

60 Diversity of Microorganisms
VI. Multicellular Animal Parasites Eukaryotes: “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.

61 Parasitic Worm in Blood
Red blood cell


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