Unit 1 Slides.pdf

HUMANS VS. MICROBES Throughout history humans have been subject to infections on a mass scale. The bubonic plague wiped out 1/3 to ½ of the entire population of Europe and Asia in less than 10 years. CHOLERA Cholera has caused at least seven pandemics in the past 200 years, killing tens of millions of people around the world. EBOLA OUTBREAKS SINCE 1976 Ebola virus disease is a more recently arisen disease that regularly has outbreaks since its discovery https://www.cdc.gov/vhf/ebola/history/distribution-map.html HUMANS VS. MICROBES US life expectancy at birth, 1900 to 2009 IN 1900, INFECTIOUS DISEASE WAS THE LEADING C AUSE OF DEATH GLOBALLY Communicable disease: An infectious disease that can be transmitted from one host to another Infectious disease: An infection (colonization on or within the body by a pathogen) that prevents the body from working normally THE “GOLDEN AGE OF MICROBIOLOGY” Better understanding of infectious disease has lead to: - Development of vaccines - Discovery of antibiotics - Public health infrastructure and therefore reduced mortality/morbidity due to infectious diseases. HUMANS VS. MICROBES Eradication of smallpox is a major public health success! - WHO-organized widespread vaccination campaign - Last case in 1977 - Now extinct “in the wild”! - only a few vials of active virus kept in storage in two secure facilities. VACCINATION AS A SUCCESS STORY Graphic by Leon Farrant http://www.behance.net/leon_far rant IMPACT ON OUR POPULATION MICROBES STRIKE BACK NEWLY EMERGING AND RE-EMERGING DISEASES Ryan White, an early victim of AIDS who contracted HIV through a blood transfusion. MICROBES STRIKE BACK NEWLY EMERGING AND RE-EMERGING DISEASES Ryan White, an early victim of AIDS who contracted HIV through a blood transfusion. MICROBES STRIKE BACK NEWLY EMERGING AND RE-EMERGING DISEASES The 2002-2003 SARS outbreak caused the World Health Organization to issue travel advisories to many cities including Toronto. MICROBES STRIKE BACK Antibiotic Resistance http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf The miracle of antibiotics meant that we finally had control over microbial infections. They were so successful that all major pharmaceutical companies discontinued antibiotic research. Now we are struggling to contain several strains of bacteria and fungi that are resistant to almost every treatment we have. WHO has declared that AMR is one of the top 10 global public health threats facing humanity. CHALLENGES • The nature of modern lives increases the likelihood of the emergence and re-emergence of diseases • Eg. Increase in the number of measles outbreaks in times of civil war, also when access to health care resources was limited due to the COVID-19 pandemic CHALLENGES: THE HEALTH GAP Data: World Health Organization CHALLENGES: THE HEALTH GAP • significant gaps in health outcomes within countries, too Ø rooted in differences in social status, income, ethnicity, gender, disability or sexual orientation • Eg. rate of tuberculosis (TB) among Inuit was over 300 times the rate of Canadian-born non-Indigenous people in 2016 • reasons for disparity are not biological reasons but social ones: such as people living in close quarters, without adequate ventilation, not receiving treatment for their active TB Tuberculosis is highly transmissible infection caused the slow-growing bacterium Mycobacterium tuberculosis. WHAT IS MICROBIOLOGY? DEFINITIONS AND TERMINOLOGY WHAT IS MICROBIOLOGY? WHAT IS MICROBIOLOGY? Microbiology is the study of organisms that are too small to be seen without a microscope WHAT ARE MICROBES? Cowan M. K. Smith H. & Lusk J. (2022). Microbiology fundamentals : a clinical approach (Fourth). McGraw Hill LLC. WHERE ARE MICROBES? Microbes are found everywhere Soil • Great diversity Ø Air Water Ø Ø 10,000 more diverse than mammalian sp. Oldest life forms on earth – longest time to evolve Vast majority unidentified WHERE ARE MICROBES? Extreme environments Deep sea vents Blood Falls – Taylor glacier Shu, WS., Huang, LN. Microbial diversity in extreme environments. Nat Rev Microbiol 20, 219–235 (2022). WHERE ARE MICROBES? Microbes are found everywhere …including on the human body MOST MICROORGANISMS ARE NOT HARMFUL …in fact, they are necessary for the existence of life on the Earth! Eg decomposition; carbon cycling MICROBES ARE ECOSYSTEM ARCHITECTS 2L 1,000,000,000 bacteria …and even more viruses Microbes are the most abundant form of life on earth NO MICROBES = NO OXYGEN TW Lyons et al. Nature 506, 307-315 (2014) doi:10.1038/nature13068 Early Earth’s atmosphere lacked oxygen for the first billion or more years. The earliest forms of life (all microbes) were able to grow without oxygen. Ø Bacteria invented photosynthesis before plants in a process that didn’t produce oxygen Ø This process evolved to one that 1) generated oxygen, and 2) was much more efficient at extracting energy from sunlight Ø Resultant ability to aerobically respire and form ozone lead to a species explosion NO MICROBES = NO AGRICULTURE "Nitrogen Cycle" by Johann Dréo, traduction de Joanjoc d'après Image:Cycle azote fr.svg. Licensed under Creative Commons Attribution-Share Alike 3.0 via Wikimedia Commons http://commons.wikimedia.org/wiki/File:Nitrogen_Cycle.svg#mediavie wer/File:Nitrogen_Cycle.svg Ø Plants and animals need organic nitrogen for the synthesis of nucleotides and proteins. Ø Air contains 70% nitrogen in the form of N2, which is useless to more complex forms of life. Ø Nitrogen fixing bacteria convert N2 to ammonia, a form of nitrogen that can be used by plants, animals, and other microbes Ø Without nitrogen-fixing bacteria higher forms of life would not have evolved in their current form. MICROBES CAN BE USEFUL Food production MICROBES CAN BE USEFUL Picture: Popular Science Monthly, June 1933 MICROBES CAN BE USEFUL Biotechnology Microbes are heavily used in biotechnology. Not only was DNA discovered because of bacteria, but almost all molecular biology labs use E. coli bacteria to clone DNA. MICROBES CAN BE USEFUL Biotechnology Insulin, a hormone used to treat diabetes was discovered in Toronto by Frederick Banting and Charles Best in 1921 used to be isolated from pigs, dogs, and cows. Girl with type-I diabetes before and 4 months after starting treatments with insulin. Insulin is now produced using recombinant DNA technology in bacteria or yeast. In 1982 it became the first recombinant protein to be used as a pharmaceutical. MICROBES CAN BE USEFUL Synthesis of commercially valuable chemicals Monosodium glutamate (MSG) is a widely used flavor enhancer. Over 1.7 million tons of MSG are produced each year – all of it by the industrial use of the bacterium Corynebacterium glutamicum, cultures of which are grown in enormous fermentation vessels. IMPACT OF MICROORGANISMS ON LIFE • Biodegradation of environmental pollutants Polychlorinated biphenyls (PCBs) Dichlorodiphenyltrichloroethane (DTT) Contaminated soil & water Oil Coolant Dry cleaning Bioremediation Cleaned Oil spill MICROBES CAN BE USEFUL Biodegradation/Bioremediation Dr. Elizabeth Edwards (University of Toronto) has been developing microbes for the purpose of bioremediation; using microbes to destroy or detoxify industrial chemicals like “PERC” at contaminated sites. Cl Cl C=C Cl Cl Perchloroethene (PCE) Dry Cleaning Solvent “PERC” H Dehalococcoides bacteria H C=C H H Ethene (harmless) Visit - http://www.labs.chem-eng.utoronto.ca/edwards/ MEDICAL MICROBIOLOGY The study of microbes that cause disease • Pathogens are microbes that can cause disease • Pathogens have shaped human history 1918 influenza killed 3 – 5% of the world’s population Saint Sebastian pleads with Jesus for the life of a gravedigger afflicted by plague during the plague of Justinian Wikipedia SUMMARY • Microbes are very old, very diverse organisms • They were essential to creating the planet as it is now and are essential for its current function • They are the most abundant cellular (bacteria) and acellular (viruses) organisms on the planet • Medical microbiology is the study of microbes that cause disease • Only a small fraction of microbes cause disease • Epidemics of infectious disease have altered the path of human civilization TYPES OF MICROBES HOW DO WE CLASSIFY ORGANISMS? Ø Humans like to classify things! Ø God created, Linnaeus organized. – Carl Linnaeus Ø The earliest ”trees of life” consisted only of two kingdoms Ø Can you guess which kingdoms? Ø Bias towards organisms that could easily be seen Ø DNA technology changed this! Ernst Haeckel’s Tree of Life, 1879. The tree of life based on the DNA sequences encoding ribosomal RNA (rDNA). 16S rRNA is highly conserved: “living record of an organisms’ history The tree can be broken into three “domains”. The bacteria, the archaea, and the eukarya (or eucarya). Tree by Norman Pace prokaryotes prokaryotes Tree of life: 2 domains!! Eukaryotes branch from Archaea Ø Used phylogenetic models that better fit the data Ø Greater sampling of prokaryotes Ø More gene families used in analysis Williams, et al. Nat Ecol Evol 4, 138–147 (2020). CLASSIFICATION OF MICROBES Microbial World Infectious agents (non-living) Organisms (living) Domain Bacteria Archaea Viruses Eucarya Viroids Prions Eukaryotes Prokaryotes (unicellular) Algae (unicellular or multicellular) Protozoa (unicellular) Protists Fungi (unicellular or multicellular) Helminths (multicellular parasites) Copyright © The McGraw-Hill Companies, Inc. CLASSIFICATION OF MICROBES Microbial World Infectious agents (non-living) Organisms (living) Domain Bacteria Viruses Archaea Viroids Prions Eucarya Eukaryotes Prokaryotes (unicellular) Algae (unicellular or multicellular) Protozoa (unicellular) Protists Fungi (unicellular or multicellular) Helminths (multicellular parasites) Copyright © The McGraw-Hill Companies, Inc. CLASSIFICATION OF MICROBES Not included in previous tree Microbial World Infectious agents (non-living) Organisms (living) Domain Bacteria Viruses Archaea Viroids Prions Eucarya Eukaryotes Prokaryotes (unicellular) Algae (unicellular or multicellular) Protozoa (unicellular) Protists Fungi (unicellular or multicellular) Helminths (multicellular parasites) Copyright © The McGraw-Hill Companies, Inc. CLASSIFICATION OF MICROBES Microbial World Infectious agents (non-living) Organisms (living) Domain Bacteria Viruses Archaea Viroids Prions Eucarya Eukaryotes Prokaryotes (unicellular) Algae (unicellular or multicellular) Protozoa (unicellular) Protists Fungi (unicellular or multicellular) Helminths (multicellular parasites) Copyright © The McGraw-Hill Companies, Inc. THE “PROKARYOTES” Ø Single-celled Ø No membrane-bound organelles Ø DNA – packed in the cytoplasm as a ‘nucleoid’ – not in a membrane bound nucleus Ø Prokaryote = “pre-nucleus” Ø Motility – have flagella that differs significantly from eukaryotic flagella Ø Multiply by binary fission Organisms (living) Bacteria Archaea Prokaryotes (unicellular) BACTERIA Ø Single-celled Ø No membrane-bound organelles Ø DNA – nucleoid Ø Rigid cell wall peptidoglycan Ø Motility – flagella Ø Multiply by binary fission BACTERIA Ø Single-celled Ø No membrane-bound organelles Ø DNA – nucleoid Ø Peptidoglycan – cell wall Ø Motility – flagella Ø Multiply by binary fission Ø Variety of shapes ARCHAEA • Archaea are prokaryotes Ø Similar size, shape, & appearance as bacteria Acidobacterium • Major differences from bacteria Ø No peptidoglycan in their cell walls Ø Ribosome more similar to eukaryotes Ø Transcription more closely resembles eukaryotes Ø Different lipids in membrane Ø rRNA sequence divergence Ø Motivation for separating Archaea from Bacteria © Dennis Kunkel Microscopy, Inc./Visuals Unlimited/Corbis ARCHAEA WERE ONLY RECOGNIZED AS ”NON-BACTERIA” IN 1977 In 1977 Carl Woese (left), based on DNA evidence, proposed that some prokaryotes, were distinct from bacteria in so many ways that they should be classified as an entirely different type of organism. Carl Woese (1928 – 2012) Initially this met with a lot of resistance but today it is accepted that Archaea are very distinct from bacteria. ARCHAEA They often live in extreme conditions (extremeophiles)… Acid mine drainage Acidophiles Hot Spring (temp, 70°C) Thermophiles www.sciencepartners.info www.photographsofthewest.org ARCHAEA …but are also part of the microbiota of all organisms Thomas, C.M et al. Factors shaping the abundance and diversity of the gut archaeome across the animal kingdom. Nat Commun 13, 3358 (2022). EUKARYOTIC CELLS ARE MORE COMPLEX THAN EITHER ARCHAEAL OR BACTERIAL CELLS generic bacterial cell (a product of 4 billion years of evolution) • Eukaryotes generic eukaryotic cell (a product of 4 billion years of evolution) Ø Cells with “true nucleus” Ø Membrane-bound organelles & nucleus FUNGI Aspergillus Microscopic or Macroscopic Single-celled Multicellular Rigid cell wall Degrade organic material © Dr. R. Kessel & Dr. G. Shih/Visuals Unlimited Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display Land Food source Yeast © CDC/Janice Haney Carr PROTOZOA Protozoa Microscopic Single-celled Paramecium Larger than prokaryotes Motile No rigid cell wall Ingest organic material Copyright © The McGraw-Hill Companies, Inc. © Manfred Kage/Peter Arnold Land Water HELMINTHS: MULTICELLULAR PARASITES Ascaris lumbricoides (roundworm) • Worm-like organisms Ø Nematodes (roundworms) Ø Cestodes (tapeworms) Ø Trematodes (flukes) • Transmission: Ø Burrow through skin Ø Consumed (food) Ø Insect bite • Complex life cycle Taenia solium (tapeworm) http://www.britannica.com Fasciola hepatica (fluke) NON-LIVING MICROBES AND INFECTIOUS AGENTS Microbial World Infectious agents (non-living) Organisms (living) Domain Bacteria Archaea Viruses Eucarya Viroids Prions Eukaryotes Prokaryotes (unicellular) Algae (unicellular or multicellular) Protozoa (unicellular) Protists Fungi (unicellular or multicellular) Helminths (multicellular parasites) Copyright © The McGraw-Hill Companies, Inc. NON-LIVING MICROBES AND INFECTIOUS AGENTS Microbial World Infectious agents (non-living) Organisms (living) Domain Bacteria Archaea Viruses Eucarya Viroids Prions Eukaryotes Prokaryotes (unicellular) Algae (unicellular or multicellular) Protozoa (unicellular) Protists Fungi (unicellular or multicellular) Helminths (multicellular parasites) Copyright © The McGraw-Hill Companies, Inc. NON-LIVING MEMBERS Tobacco mosaic virus Viruses Ø Obligate intracellular parasite Ø i.e., inactive outside host © K.G. Murti/Visuals Unlimited Ø Multiply using host machinery Ø Infected cells – “hosts” Influenza virus © Thomas Broker/Phototake Ø Nucleic acid genome housed by protein coat Ø Infect all life forms Bacteriophage © K.G. Murti/Visuals Unlimited Copyright © The McGraw-Hill Companies, Inc. NON-LIVING MEMBERS Prions • Infectious protein Ø Consist of protein, no DNA or RNA Scrapie • Causes normal proteins to misfold • Misfolded aggregation of proteins – “Fibrils” Ø Found in brain • Proteins lose normal function Ø Cells unable to function • Resistant to standard sterilization procedures Scrapie is a cause of neurodegenerative disease in sheep SUMMARY • The “tree of life” is best fit by two domains, Bacteria and Archaea Ø Eukarya have branched off of Archaea Ø Genetic information has been instrumental in defining the tree of life • The microbial world is composed of cellular (living) and acellular (non-living) • There are distinct features of Bacteria, Archaea and Eukarya • The Eukaryotic organisms studied by microbiologists (Fungi, Algae, Protozoa and Helminths) are very diverse www.genomicenterprise.com PRE-GERM THEORY: MIASMA THEORY OF DISEASE • The prevalent theory of disease from ancient Greece till the mid of 19th century • Miasmas are poisonous emanations, from putrefying carcasses, rotting vegetation or molds, and invisible dust particles ➢ believed that the miasma would enter the body and cause diseases like cholera and malaria DISCOVERING MICROBES Prior to being able to see microbes, there were scholars who suggested they exist • 5th century, BC: Jain scriptures describe nigodas, sub-microscopic creatures living in large clusters, having a very short life and pervade every part of the universe, even in tissues of plants and animals • 1400s: Turkish scientist Akshamsaddin claimed that diseases, like plants and animals, have “invisible seeds” This simple microscope was able to magnify things 300x! DISPROVING SPONTANEOUS GENERATION 1861 Pasteur shows that microbes do not grow in liquid until introduced from outside — even with air, non-life cannot create life • Pioneer of antiseptic surgery • Inspired by Pasteur’s work on fermentation • wondered if “minute organisms” responsible for pus in wounds • “It is a common observation that, when some injury is received without the skin being broken, the patient invariably recovers,” he once told his medical students. “On the other hand, trouble of the gravest kind is always apt to follow, even in trivial injuries, when a wound of the skin is present. How is this?” • Added carbolic acid directly to wounds and found it prevented infections • Later developed other methods to exclude bacteria from wounds: • Sterilizing instruments before use • Clean operating room ROBERT KOCH (1843 – 1910): IDENTIFYING DISEASE CAUSING ORGANISM * * not the case for many viruses (eg HIV) viruses need a host to grow * * differing responses between hosts eg COVID animal models of disease… SUMMARY • Miasma theory was prevalent for a very long time in history and solid evidence was not enough at first to get physicians to accept Germ Theory • Acceptance of Germ Theory was aided by several experiments and factors eg the ability to visualize microbes • Without knowing the cause of disease, Semmelweis and Lister inferred that non-hygienic practices were contributing to mortality rates when the skin was broken • Pasteur’s (and others’) experiments disproving spontaneous generation of microbes helped support Germ Theory • Koch developed postulates to support the identification of the causative agent of disease

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