Chapter 1: A Brief History of Microbiology

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

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.

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

Penicillin is Produced by a Mold

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

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).

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.

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.

Infectious Diseases Causing Most Deaths Worldwide in 2000 Disease Cause Deaths/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.

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

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.

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

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

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 1500-1700.

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

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.

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.

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

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.

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 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.

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

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

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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

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

Kingdom Prokaryotae: Bacteria lack nucleus and membrane bound organelles

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

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 Brownian motion.

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.

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.

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

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

Diversity of Microorganisms III. Protozoa (Sing. Protozoan) Classified based on locomotion: Flagella: Long whip like appendages. Example: Trichomonas vaginalis, 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.

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.

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.

Comparison of Cells and Viruses

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.