INTRODUCTION TO MEDICAL MICROBIOLOGY

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INTRODUCTION TO MEDICAL MICROBIOLOGY
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What is microbiology?

• Bacteriology
• Virology
• Mycology
• Immunology
• Genetics

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Historical Perspective

• 1200 A.D. The Plague or Black Death
• culprit Yersinia pestis. Transmitted from the
  fleas that lived on the rats that lived with the
  humans and defecated in grain stores. Human to
  human transmission also possible.
• 2/3 of the population of western Europe perished
  (The REALLY Dark Ages!)
• Hooke 1665- cells in cork

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Historical perspective

• Van Leeuwenhoek 1674 optician. Viewed
  Bacillus anthracis among others.
• Edward Jenner 1796- First successful
  vaccination.
• Relationship of cowpox to smallpox
• Smallpox (virus)
• 30-40 mortality
• Viremia followed by death
• Last naturally occurring case in Africa, 1976.
• Role of WHO in smallpox eradication
• Possible because humans are the only smallpox
  host.

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Historical Perspective

• So, where are we now?
• Who is immune?
• Possibility of bioterrorism.
• Todays plan Immunize first responders, then
  public.

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• Schwann 1839- The Cell Theory
• All organisms are made up of cells
• The cell is the basic organizational unit of life
• Cells cannot arise de novo.

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Historical Perspective

• Snow 1853 First successful epidemiological
  study.
• Culprit Vibrio cholerae, contaminating a water
  pump on Broad Street in London. Actual raw
  sewage into drinking water. Closed down the pump
  epidemic over.
• Cholera still responsible for tens of thousands
  of deaths a year.

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Historical Perspective

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Louis Pasteur

• Redi 1800. Disproved theory of spontaneous
  generation which said that living organisms can
  arise from dead matter, e.g. maggots on dead
  horseflesh. Said maggots came from eggs of
  flies, not meat. Still, no one believed him.
• Pasteur 1861. Figure 1.2. Basically, air
  contains microorganisms. Made sterile solutions
  by using cotton plugs. Plug captures bacteria
  and can then be used to inoculate sterile
  infusions.
• Also used a swan flask to disprove the vital
  force theory that the infusions themselves had
  the ability to capture the bacteria.

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Historical Perspective
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Pasteur (cont)

• 1864 -Pasteurization of wine
• Immunoprophylaxis for rabies
• Described fermentation pathway of sugar to
  ethanol and carbon dioxide in an anaerobic
  environment.
• Lister 1867 Study of childbed fever in a
  London lying-in hospital.
• Aseptic technique

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Historical Perspective

• Koch 1876- Linked anthrax to a bacterium
• Kochs Postulates
• Microorganism must be present in every case of
  the disease
• Organism must be grown in pure culture from the
  diseased host
• Inoculation of above into host must give same
  disease
• Organism must be recovered from experimentally
  infected host
• Also presented methods of obtaining pure cultures
• Found the cause of tuberculosis is the bacterium
  Mycobacterium tuberculosis.

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Historical Perspective

• Gram Stain 1884
• 1892 - Filterable agent in tobacco mosaic disease
  a virus
• 1911 Rous sarcoma virus (a retrovirus) can
  cause cancer in chickens.
• Other virus/cancer links (circa 1966 Huggins
  and Rous)
• HIV _ Kaposis sarcoma
• HPV Cervical cancer
• Hepatitis B- Liver cancer

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Historical Perspective

• 1917-1921. Influenza Pandemic. Best estimates
  are 25 30 million confirmed dead, millions more
  suspected.
• 1908-1919 The Golden Age of Immunology
• Mechnikov immune response and macrophages
• Carrell organ transplantation
• Bordet 2 types of immunity
• Vaccines for (1950-1960)
• Rubella
• Measles
• Mumps

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Historical Perspective

• Griffith 1928 The Transforming Principle (p.
  206)
• Experiment to determine which part of a
  pneumococcus bacteria caused the disease.
• 1944 Its the DNA, not the capsule, not the
  cytoplasm. Provided the groundwork for Avery and
  McLeods definitive work, as well as for Watson
  and Crick
• Fleming 1945 Penicillin (beta lactam ring in
  outer layer of a bacteria is inhibited, making
  cell wall synthesis impossible)

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Historical Perspective

• Landsteiner 1930 ABO Human blood groups 6
  genotypes, 4 phenotypes
• 1939 Domagk Sulfa drugs inhibit folic acid
  synthesis.
• Theiler 1951- Vaccine (live, attenuated)
  against yellow fever, a virus
• Beadle, Tatum, and Lederberg 1958. One gene,
  one enzyme hypothesis.
• The Central Dogma dsDNA to ssmRNA to amino
  acids to polypeptide to protein.
• Since modified to the one gene/one polypeptide
  hypothesis due to redundant enzymes.

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• Salk and Sabin 1950s Vaccine for the virus
  that causes poliomyelitis. Both are live,
  inactivated vaccines. Sabin currently used in
  U.S.

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Historical Perspective

• 1940-1970 Golden Age of Bacteriology. 2
  pronged attack with vaccines and antibiotics.
• Diptheria
• Pertussis
• Tetanus
• Haemophilus influenza
• 1952 Waksman streptomycin another B lactam
  drug.

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Historical Perspective

• 1953 Watson, Crick, Franklin, and Wilkins
• The structure of DNA
• 4 nucleotides 2 purines (A and G) and 2
  pyrimidines (C and T).
• Name origin (tissue each base was isolated from)
• Adenine from pancreas
• Guanine from bird guano
• Thymine from thymus gland
• Cytosine from cells
• Base covalently bonded to 5 carbon sugar
  molecule, which is then bonded to a phosphate
  molecule
• Joined by phosphodiester bond

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Historical Perspective

• Hershey 1969- Structure and replication of a
  bacteriophage. By definition, this is a virus
  that infects a bacterium
• Edelman and Porter 1971 Structure of the 5
  major classes of immunoglobulins (aka antibodies)
• 2 heavy and 2 light chains the antigen binding
  site found near the variable region of both the
  light and heavy chain complement activation at
  the Fc region disulfide bonds holding all 4
  chains together

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Classes

• IgG 80 of total serum globulins. Works via
  opsonization and or aggultination and
  precipitation of antigen/antibody molecule
• IgM 5-10. First antibody. Important in
  recognizing antigens
• IgA 10-13. Found in secretions (e.g. breast
  milk, tears, saliva)
• IgD 1. Found on surface of mature beta cells.
  Function unknown.
• IgE ,1. Important in allergic reactions, e.g.
  asthma, hayfever, anaphylaxis.

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Historical Perspective

• Baltimore 1971 Discovered reverse
  transcriptase.
• Modified Central Dogma ssRNA made into dsDNA
  (via this enzyme) into mRNA to amino acids
• Boyer 1973 First to clone DNA using a plasmid
• 1976 Legionaires Disease, Philadelphia
• Yalow 1977 Discovered prions in kuru. Newly
  important in Mad cow disease

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Historical Perspective

• Nathans 1978 Used restriction enzymes to map
  viral genomes
• McClintock 1983 Transposons pieces of DNA
  that move freely within and between other cells.
• 1979 First cases of Kaposis sarcoma and
  Pneumocystis carinnii in U.S.
• Montagnier and Gallo 1983 Isolation of HTLV
  III, now known as HIV.

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Historical Perspective

• 1989 -Emergence of Hantavirus
• 1999- Completion of the Human Genome Project
• 2000 - First new antibiotic to market in 35 years
  (Zyvox)
• 2001 Bioterrorism in the U.S. (anthrax letters)