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Unformatted text preview: MMG 461: Molecular Pathogenesis M. H. Mulks January 7, 2008 Dr. Martha Mulks 5193 BPS 355-6463 X1574 [email protected] Dr. Cindy Arvidson 5192 BPS 355-6463 X1573 [email protected] Dr. Hilary Phelps 5107 BPS 355-6463 X1544 [email protected] Textbook
q Abigail A. Salyers & Dixie D. Whitt. 2002. Bacterial Pathogenesis: A Molecular Approach, 2nd. Ed. ASM Press, Washington, DC. Also assigned readings from primary literature, which will be posted on ANGEL q Exams
Exam 1 q Exam 2 q Exam 3 q Final Exam
q q Mon. Feb. 4 Wed. Mar. 12 Wed. Apr. 9 Mon. Apr. 28 20% 20% 20% 40% Exams will include both multiple choice and short answer essay questions. ANGEL Web-site
q Course syllabus with lecture schedule and reading assignments is available on the ANGEL web-site, which will also be used for course announcements. PowerPoint files for each lecture will be posted on ANGEL the day before the lecture. q A BRIEF HISTORY OF MEDICAL MICROBIOLOGY
1674 1678 1798 1876 1878 1884 Antonie van Leeuwenhoek develops the single lens microscope. Robert Hooke develops the compound microscope. Edward Jenner develops a vaccine for small pox. Robert Koch proposes the germ theory of disease (Koch's postulates). Joseph Lister develops the first pure culture techniques. Hans Christian Gram develops the gram stain for bacteria. A BRIEF HISTORY OF MEDICAL MICROBIOLOGY
1879-1910 Identification of many major bacterial pathogens, including the agents of anthrax, diphtheria, typhoid, gonorrhea, gangrene, tetanus, syphilis 1920-1960s An era when many major infectious diseases were defeated, due to parallel developments of antibiotics and vaccines - Vaccines against diphtheria, tetanus, measles, mumps, polio, rubella, etc. - Penicillin, sulfonamides, tetracyclines, etc. A BRIEF HISTORY OF MEDICAL MICROBIOLOGY
1970s 1971 1973 1975 1977 NOW Development of a new set of tools for molecular studies of disease Nathans, Smith, and Arber describe restriction enzymes. Berg, Boyer, and Cohen lay the groundwork for genetic engineering. Kohler and Milstein develop methods to produce monoclonal antibodies. Maxam and Gilbert describe a method to sequence DNA. Genomes of many bacterial pathogens have been sequenced, and the human genome sequence is now available Major causes of death in the US - 1900
q q q q q q q q q q Pneumonia & influenza Tuberculosis Diarrhea, enteritis, intestinal infections Heart disease Cerebrovascular disease Kidney disease, nephritis Accidents Cancer Senility Diphtheria
Rates per 100,000 population 202.2 194.4 142.7 137.4 106.9 88.6 72.3 64.0 50.2 40.3 Major causes of death in the US - 2000
q q q q q q q q q q q q q q q Heart disease Cancer Cerebrovascular disease Chronic obstructive pulmonary disease Accident Pneumonia & influenza Diabetes Suicide Kidney disease Chronic liver disease & cirrhosis Alzheimer's Septicemia Homicide HIV Atherosclerosis 130.5 125.5 25.9 21.1 30.1 12.9 13.5 10.6 4.4 7.4 2.7 4.2 8.0 5.8 2.1 Rates per 100,000 population, age-adjusted to the 1940 US population Have we or are we about to wipe infectious diseases from the face of the earth?
q A recent review identified 1415 species of infectious organism known to be pathogenic for humans
q q q q q 217 viruses and prions 538 bacteria 307 fungi 66 protozoa 287 helminths Have we or are we about to wipe infectious diseases from the face of the earth?
q q q q q The only infectious disease that has been eradicated to date is small pox New diseases and new pathogens are still being recognized, such as Legionnaire's disease (1976), Lyme disease (1977), toxic shock syndrome (1980) AIDS (1980), hantavirus pulmonary syndrome (1994), SARS (2003), Helicobacter pylori, Chlamydia pneumoniae, etc. Old infectious diseases are resurging, such as TB Many diseases have proven refractory to vaccine development, such as STDs Antibiotic resistance has become a major concern Notifiable disease = A notifiable disease is one for which regular, frequent, and timely information regarding individual cases is considered necessary for the prevention and control of the disease. State public health departments and the US Centers for Disease Control are notified. Incidence of selected notifiable diseases in the US
q q q q q q q q q q q q q q q q q q q Cases 2005 AIDS 41,120 Botulism 135 Chlamydia 976,445 Diphtheria 0 Encephalitis, West Nile 3,000 EHEC & STEC E. coli 3,629 Gonorrhea 339,593 Legionellosis 2,301 Lyme disease 23,305 Measles 66 Meningococcal disease 1,245 Mumps 314 Pertussis 25,616 Salmonellosis 45,322 Shigellosis 16,168 Syphilis (primary & secondary) 8,724 Tetanus 27 Toxic shock syndrome 90 Tuberculosis 14,097 Deaths 2001 14,175 3 0 0 NA 6 7 70 2 1 199 0 17 40 2 36 5 75 764 What does pathogenesis mean? Pathogenesis = the origination and development of a disease Disease = an abnormal condition that impairs bodily functions What is a pathogen? Pathogen = an organism capable of causing disease in a particular host Primary or principal pathogen Opportunistic pathogen Pathogenicity = the ability to cause disease Virulence = degree of pathogenicity Avirulent Virulence factor = property (gene product) that enhances the ability of a microorganism to cause disease How do we know which pathogens cause specific diseases, and which virulence factors contribute to the disease process? Koch's Postulates
q The organism must always be found in the diseased animals (tissues) but not in healthy ones. The organism must be isolated from diseased animals and grown in pure culture away from the animal. The organism isolated in pure culture must initiate and reproduce the disease when reinoculated into susceptible animals. The organism should be reisolated from experimentally infected animals. These are the criteria, outlined by Robert Koch in 1877 in his study of anthrax, used to prove that a specific microorganism is the causative agent of a specific disease. q q q q Modified Koch's Postulates for Molecular Biology
q q The gene must be identified from a virulent microorganism. The gene must be inactivated by methods which do not allow reversion. The inactivated gene must be introduced into the original strain in such a way as to replace the wild type gene, constructing an isogenic strain that is negative for that gene. The strain with the inactivated gene must be shown to be avirulent or to have measurably reduced virulence. Reintroduction of the wild type gene into the isogenic negative strain should lead to a return to original virulence. These criteria can be used to provide proof that a specific gene and gene product contribute to the virulence of a pathogenic organism. q q q q How do you measure virulence?
q ID50 = number of bacteria necessary to infect 50% of the exposed animals LD50 = number of bacteria necessary to kill 50% of the exposed animals Competitive assays q q "Be fruitful and multiply." A pathogen that kills its host without spreading to additional hosts has committed suicide, which is not a very successful strategy. The traditional infectious cycle
Entry of the pathogen q Colonization: establishment and multiplication q Avoidance of host defenses q Damage to the host = disease q Exit
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This note was uploaded on 03/19/2008 for the course MMG 461 taught by Professor 3 during the Spring '08 term at Western Michigan.
- Spring '08