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BIOL 314 Medical Microbiology Winter Term 1 2024 (2024WT1) Instructor: Dr. Jose Sapien, MD (He, his, him) [email protected] SCI 161 UBC Okanagan is on Syilx Okanagan Nation Land We respectfully acknowledge that the UBC Okanagan campus is situated on the traditional, ancestral, and unceded territ...

BIOL 314 Medical Microbiology Winter Term 1 2024 (2024WT1) Instructor: Dr. Jose Sapien, MD (He, his, him) [email protected] SCI 161 UBC Okanagan is on Syilx Okanagan Nation Land We respectfully acknowledge that the UBC Okanagan campus is situated on the traditional, ancestral, and unceded territory of the Syilx Okanagan Nation and their peoples. For more information please see: https://ok.ubc.ca/about/indigenous- engagement/. 2 About me… Degree Previous work Previous research Previous teaching Hobbies 3 Medical Microbiology BIOL 314 Introduction Copyright © 2021 W. W. Norton & Company, Inc. Course Information ▪ Winter Term 1 2024 (2024WT1) ▪ Start Sept 03 2024 – End Dec 05 2024 ▪ Tuesday and Thursday 12:30 PM - 2:00 PM ▪ ART 366 ▪ Course format: Lecture (2 x 80min/wk). ▪ Office location & office hours: SCI 161(Wed 12:00 – 13:00 - appointment is preferred) 5 Course Description ▪ Introduction into the pathogenesis of human infectious diseases and the microbiology of the infectious agents. ▪ Prerequisite: BIOL 228 ▪ Co-requisites: BIOL 318 6 Course Structure ▪ In person (Only in necessary cases, and previous notice, we could conduct the class online). ▪ Check your Canvas regularly for deadline activities. ▪ Scheduled lecture times will be used for in-class lectures, discussions and tests. ▪ Lecture PowerPoints - same lecture day. Therefore, pre-reading the lecture subject is necessary. ▪ All material from these presentations, all material discussed, and all assigned readings are examinable. 7 Course evaluation Every 2 weeks Tuesdays ~ 7 in total Last 30 min. of class Course materials ▪ Respondus Lockdown Browser installed and ready to work. ▪ UBC Canvas page ▪ iClicker Cloud app ▪ Textbook: “Microbiology: The Human Experience”, 2nd Ed. by John Foster, Zarrintaj Aliabadi, and Joan Slonczewski. ▪ Norton Digital Landing Page CHAPTER 1 Microbes Shape Our History Copyright © 2021 W. W. Norton & Company, Inc. Objectives ▪ Describe the discovery of microbes related to human health, including the tools of microscopy and medical statistics. ▪ Explain Koch’s postulates for showing that a microbe causes disease. ▪ Describe how environmental microbes are essential for human life. 2 Half a Lung Is Better Than None – 1 Scenario ▪ Debi was an ordinary teenager attending an affluent American public high school when she contracted tuberculosis (TB). She did not know the person who infected her. Infection requires inhalation of the causative bacteria. 3 Half a Lung Is Better Than None – 2 Signs and Symptoms ▪ For several weeks, Debi coughed all the time, felt tired, and was losing weight. ▪ Her coughing brought up blood. ▪ An X-ray revealed the signs of infection in her lung, including a large hole eaten away by the bacteria. 4 Half a Lung Is Better Than None – 3 Diagnosis ▪ From Debi’s sputum sample, a DNA sequence was amplified by PCR (polymerase chain reaction). ▪ The DNA sequence revealed Mycobacterium tuberculosis, the cause of TB. 5 Half a Lung Is Better Than None – 4 Treatment ▪ Doctors prescribed isoniazid and rifampin, antibiotics that kill most strains of M. tuberculosis. But Debi’s TB strain proved resistant to nearly all known drugs (MDR-TB, multidrug-resistant TB). ▪ Because drugs failed to eliminate the MDR strain, Debi had to have nearly half of her right lung removed. 6 Half a Lung Is Better Than None – 5 Follow-up ▪ All the teachers and students in Debi’s school were screened, and over 200 were found to have been infected by a student with tuberculosis misdiagnosed for 2 years. All required treatment to prevent disease. 7 1.1 From Germ to Genome: What Is a Microbe? – 1 Section Objectives ▪ Describe how we define a microbe, and explain why the definition is a challenge. ▪ Describe the three major domains of life: archaea, bacteria, and eukarya. Explain what the three domains have in common and how they differ. ▪ Define viruses, and explain how they relate to living cells. 8 1.1 From Germ to Genome: What Is a Microbe? – 2 ▪ Where did life come from? Earth’s earliest life forms were microscopic cells. These single cells gradually evolved into more complex cells and multicellular organisms like plants and animals. 9 Microbes are critical in maintaining our environment. They – fix nitrogen into forms used by plants. – produce vitamins humans consume. – serve as primary producers in food webs. Microbes are critical to human health and wellness. A small or large number act as pathogens and causing disease? A Microbe Is a Microscopic Organism ▪ A microbe is commonly defined as a living organism that requires a microscope to be seen. ▪ A cell is the smallest unit of life composed of a membrane-enclosed compartment. Microbial cells range in size from millimeters to 0.2 micrometers. Viruses are noncellular microbes that can be up to ten times smaller than a cell. 12 Different Kinds of Microbes – 1 ▪ Microbes are classified as members of a species according to a shared set of genes and traits. (like other organisms) The scientific name of a species is italicized and includes a capitalized genus name followed by a lowercase species name; for example, Staphylococcus aureus. ▪ Microbes are classified by their genetic relatedness determined by comparing microbial genomes. The genome is the total DNA content of an organism. Viral genomes can be RNA or DNA? Different Kinds of Microbes – 2 ▪ Microbial cells may be Methanocaldococcus jannaschii, an archaeon Prokaryotic that produces methane. – No true “nucleus” or nuclear membrane – Prokaryotes include bacteria and archaea. Eukaryotic Pelomyxa sp., a large ameba. – Have a true nucleus – Eukaryotic microbes include some types of fungi, protozoa, and algae. 14 Different Kinds of Microbes – 3 ▪ What about viruses? Noncellular Nonmetabolic Unable to reproduce independently – Invade cells, which produces new viruses Are viruses even “alive”? Human papillomavirus is the cause of genital warts and cervical or penile cancer (model based on electron microscopy). 15 ▪ What microbe is considered a A. Bacteria? parasite? B. Virus? C. Worms? D. Fungi? E. All of the above? F. None of the above? 1.2 Microbes Shape Human History Section Objectives ▪ Explain how microbial diseases have changed human history. 17 Microbial Diseases Devastate Human Populations ▪ Throughout history, microbial diseases such as tuberculosis and leprosy have profoundly affected human demographics and cultural practices. ▪ Before the 1850s the role of microbes as infectious agents was unknown. Figure 1.3A Microbial Disease in History and Culture A. Medieval church procession to ward off the Black Death (bubonic plague). 18 Microscopes Reveal the Microbial World – 1 ▪ Robert Hooke built the first compound microscope. ▪ Published his illustrations of these materials in Micrographia (1665), the first publication that illustrated objects observed under a microscope ▪ He called distinct units of living material “cells.” ▪ Monk cells in Rila Monastery, Bulgaria. From: https://travellingbuzz.com/rila-monastery/ 19 Microscopes Reveal the Microbial World – 2 ▪ Anton van Leeuwenhoek observed bacteria with a single-lens microscope. ▪ It took nearly 200 years before a connection was made between microbes and human diseases. 20 Spontaneous Generation: Do Microbes Have Parents? ▪ Spontaneous generation, the theory that microbes can arise spontaneously, was debated throughout the eighteenth century. ▪ Louis Pasteur proved that bacteria were living things capable of reproducing and potentially acting as a cause of disease. 21 1.3 Medical Microbiology and Immunology Section Objectives ▪ Define the germ theory of disease. ▪ Explain how Florence Nightingale first drew a statistical correlation between infectious diseases and human mortality. ▪ Explain how Koch’s postulates can show that a specific kind of microbe causes a disease. Explain the problems in interpreting Koch’s postulates in practice. 22 Linking Infectious Disease with Mortality – 1 ▪ Germ Theory of Disease The connection between the tools of microscopy, microbial culture, and statistical analysis. 23 Linking Infectious Disease with Mortality – 1 ▪ Germ Theory of Disease Florence Nightingale, Founder Specific diseases are caused by of Modern Nursing microscopic “germs.” and Medical Statistics Disease is common in overcrowded areas like cities and during warfare. Florence Nightingale demonstrated the statistical significance of mortality due to infectious disease. 24 Linking Infectious Disease with Mortality – 2 ▪ The field of public health assesses the role of infectious disease in the health of populations. ▪ Epidemiologists use statistics to determine the cause of disease using methods first implemented by Nightingale. ▪ In Canada, the Public Health Agency of Canada (PHAC) plays a central role in monitoring and responding to public health threats, conducting research, and providing public health guidance and information to Canadians. 25 Growth of Microbes in Pure Culture ▪ Diagnosis requires direct evidence that a given microbe caused the disease. Robert Koch worked on this problem in the nineteenth century. ▪ This principle of epidemiology is called the chain of infection/transmission of disease. ▪ Pure cultures grown from a single colony of bacteria were crucial tools for Koch. 27 Koch’s Postulates Link a Pathogen with a Disease – 1 ▪ Koch developed the first scientific method for establishing the microbial cause of a disease. ▪ Koch’s postulates link a pathogen with a disease. 28 Koch’s Postulates Link a Pathogen with a Disease – 3 ▪ Koch’s postulates can’t always be applied to identify the cause of a disease. M. tuberculosis causes symptoms in only 10 percent of people infected. HIV is difficult to detect in early stages and is an exclusively human pathogen. Therefore, following the postulates would involve infecting human subjects with HIV…ethical? 29 Immunization Prevents Disease – 1 ▪ By 1000 BCE in India and China, exposing a person to fluids from a pox pustule was being used to prevent deaths from smallpox. ▪ In the eighteenth century, Lady Mary Wortley Montagu, pox survivor and wife of the British Ambassador, brought the practice to England. 30 Immunization Prevents Disease – 2 ▪ To decrease the risk of serious disease that occurred with human smallpox exposure, Dr. Edward Jenner used fluid from cowpox instead of human smallpox. ▪ Cowpox inoculation was called vaccination. 31 Immunization Prevents Disease – 3 ▪ Louis Pasteur showed that exposure to attenuated (weakened) strains of bacteria conferred immunity to a disease without causing severe symptoms. ▪ Heat treatment or aging for various periods often turned out to be the most effective approach. 32 Antiseptics and Antibiotics Control Pathogens – 1 ▪ Knowing that “germs” caused disease in humans led to breakthroughs in disease prevention. Ignaz Semmelweis suggested that the use of antiseptics by doctors could protect patients. From: https://ciencia.unam.mx/leer/986/coronavirus-ignaz-semmelweis-y-la-costumbre-de-lavarse-las-manos 33 Joseph Lister used chemical treatment of surgical instruments to prevent transmission. – These discoveries led to the use of aseptic (carbolic acid) operating rooms. Antiseptics and Antibiotics Control Pathogens – 2 ▪ Alexander Fleming noted a mold growing in one of his cultures killed bacteria growing around it. ▪ Chemists Florey and Chain purified the chemical the mold produced. ▪ Mass production of penicillin gave birth to the pharmaceutical industry. 35 The Discovery of Viruses – 1 ▪ Early germ-hunters noted that some contagious diseases were “filterable” and therefore could not be bacterial cells. o ▪ “Infective particles” causing a disease in tobacco plants were crystallized by Wendell Stanley and called “tobacco mosaic virus” (TMV). 36 The Discovery of Viruses – 2 Tobacco mosaic virus (TMV). The RNA Herpesvirus structure. 3D structure of chromosome is surrounded by protein subunits. herpes simplex virus type 1. 37 1.4 Microbes in Our Environment Section Objectives ▪ Explain how mitochondria and chloroplasts evolved by endosymbiosis. 38 Animals and Plants Evolved through Endosymbiosis ▪ Lynn Margulis first proposed that the energy-converting organelles of eukaryotic cells (mitochondria and chloroplasts) evolved as a result of endosymbiosis. 39 New Microbes Continue to Emerge ▪ In 1977, Carl Woese first proposed a “new” form of prokaryotic life called archaea, with characteristics distinct from other bacteria and from eukaryotic life. 40 Clicker Question 1 You discover a microbe that lacks a nuclear membrane. You found the microbe growing in the boiling sulfur springs in Yellowstone. Based on the cell structure and extreme environment, you hypothesize that the microbe is most likely a. a bacterial cell. b. a protozoan. c. a fungal cell. d. an archaeon. e. a virus. 41 Clicker Question 2 Which of the following is characteristic of a virus? a. Viruses are prokaryotic in cell design. b. The cell wall of a virus is similar to that of plants. c. Viruses are unable to reproduce independently. d. Viral genomes are made solely of DNA. 42 Clicker Question 3 Assume that the theory of spontaneous generation is TRUE. Predict the result if you were to repeat Pasteur’s experiment shown below. a. Microbes would grow in the flask. b. Microbes would not grow in the flask. c. The answer cannot be determined from the information provided. 43 Clicker Question 4 You are attempting to prove that bacterium A causes a respiratory disease in your laboratory mice. You have isolated the bacterium from sick mice and grown the bacterium in pure culture. What is the next step you would take to fulfill Koch’s postulates? a. Determine the shape of the bacteria using a microscope. b. Sequence the bacterial genome. c. Inoculate healthy laboratory mice with the pure culture. d. Vaccinate healthy laboratory mice against the bacterium. e. Isolate the same bacterium from healthy laboratory mice. 44 Clicker Question 5 Which type of relationship between cells led to the evolution of eukaryotes and multicellular life? a. commensalism b. endosymbiosis c. pinocytosis d. epigenesis 45 Clicker Question 6 Which of the following statements about bacteria and archaea is true? a. Bacteria and archaea are multicellular microbes. b. The cells of both bacteria and archaea are prokaryotic in design. c. DNA sequence analysis shows that bacteria and archaea are genetically the same. d. Archaea are different from bacteria in that archaea have nucleated cells. 46 ▪ https://ncia.wwnorton.com/124416 TA information ▪ Serena Jilani ▪ Second-year Master's student in the Biochemistry and Molecular Biology program. ▪ Questions? → [email protected] TA information ▪ Serena Jilani ▪ Second-year Master's student in the Biochemistry and Molecular Biology program. ▪ Questions? → [email protected]

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medical microbiology infectious diseases pathogenesis
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