BIOL121 Lecture 3 2023-24.pptx

BIOL121 Lecture 3 Bacterial Pathogenicity HOW BACTERIA CAUSE DISEASE Professor Roger Pickup Session code : 423374 Recommended reading: Campbell, chapter 27.6. Introduction to chapter 47 More detail: Brock, chapter 23 (focus on latter half of chapter on pathogenesis and host factors) Learning Objec...

BIOL121 Lecture 3 Bacterial Pathogenicity HOW BACTERIA CAUSE DISEASE Professor Roger Pickup Session code : 423374 Recommended reading: Campbell, chapter 27.6. Introduction to chapter 47 More detail: Brock, chapter 23 (focus on latter half of chapter on pathogenesis and host factors) Learning Objectives After this lecture and the further reading you should be able to: • sequence the events involved in the establishment of bacterial infection • describe some of the key bacterial factors involved in host colonization and tissue damage Specific Learning objectives • Define pathogenicity and virulence • Understand the role of reservoirs and how pathogens are transferred between hosts • Differentiate between opportunistic and primary pathogens • Give an overview of Colonisation Adherence Role of Iron Barriers to infection in the body Invasion Brief introduction to host defences e.g. antibodies and phagocytes – Endotoxins and exotoxins – – – – – – Most bacteria are harmless • Bacteria are ubiquitous in the environment food, soil, water, normal human microbiota • Vast majority are harmless - very few pathogenic • Host immune system very efficient at preventing most bacteria from causing disease: >1014 (100,000,000,000,000) bacteria live in and on our body (= normal microbial biota) Host – Pathogen Interaction Definitions: • Host: organism which supports growth of viruses, bacteria and parasites • Pathogen: organism that causes disease, by impairing or interfering with the normal physiological activities of the host • Pathogenicity: the ability to cause disease • Virulence: the degree or intensity of pathogenicity (determined by toxicity and invasiveness) Virulence From Brock Infection or disease? • Infection: bacteria persist in host without necessarily causing tissue damage • Disease: overt damage to the host, parts of body cannot fulfill their normal functions HEALTH INFECTIO N DISEASE Germ vs Miasma theory in the mid 1800s • Miasma theory-’bad air’ origin of epidemics from rotting organic matter; get rid of the smells you get rid of the illness such as cholera or ‘plague’ • Eradication of disease through the preventive approach of cleansing and scouring. • One prominent supporter of the miasma theory was Dr. William Farr. He was convinced that cholera was transmitted by air. • Soil at low elevations, especially near the banks of the River Thames, contained much organic matter which produces ‘miasmata’. The concentration of such deadly ‘miasmata’ would be greater at lower down than in the surrounding hills. Robert Koch (18431910) • What is the nature of infectious disease? Microbes were “suspects” but proof was lacking! • Koch’s lab established germ theory of disease. • Formulated criteria for proving that a specific microorganism causes diseases: “Koch’s Postulates” • Developed simple methods for obtaining bacteria in pure culture Koch’s Postulates • • Led to discovery of the causes for: Anthrax, Tuberculosis, Cholera Koch awarded Noble prize for Physiology and Medicine (1905) Successful bacterial pathogens Divided into two broad groups: 1. Opportunistic pathogens Only cause serious disease when host defences are impaired – e.g. Pseudomonas aeruginosa . Often exist in the environment 2. Primary pathogens (Obligate) Capable of causing disease in absence of immune defects e.g. Treponema pallidum -syphilis Need to cause disease to survive human-human transmission Animal-human transmission (zoonotic) Steps in infectious disease 1 Reservoir Transport to host Tissue damage Adherence & Colonisation Invasion of tissues Evasion of host defense Reservoirs • Bacterial pathogens must have at least one reservoir: – • Other humans • Animals • Environment Reservoirs: examples Disease Anthrax Agent Bacillus anthracis Legionnaire’ Legionella s Disease pneumophi la Chlamydia Chlamydia trachomati s Reservoir Livestock, soil High moisture environments e.g. air-con systems, water tanks Humans Transfer to host may be direct Transfer to host • Direct host-to-host transmission • Airborne: aerosols (coughing and sneezing) • Body contact: touching, kissing, sexual intercourse • Indirect host-to-host transmission • Vector-borne transmission: vector = living organism - arthropods (insects, ticks, mites) - vertebrates (rats, dogs, cats, bats, birds …) Zoonosis • Vehicles: non-living materials or objects Steps in infectious disease 2 Reservoir Transport to host Tissue damage Adherence & Colonisation Invasion of tissues Evasion of host defense Colonisation • Colonisation: establishment of a stable population of bacteria in the host • The human body contains a large number of bacteria (microflora = microbiota) • The pathogen must be able to compete successfully for nutrients Adherence 1 • To overcome flushing mechanisms bacteria must adhere to host cell surfaces • Some bacteria adhere to other surfaces, – streptococci to tooth surfaces – Staphylococci to plastic catheters or shunts Adherence 2 1st stage: Association Involves non-specific forces (e.g. charge and hydrophobicity) 2nd stage: Adhesion Involves specific bacterial adhesins and host receptors • Subsequent stages may result in aggregation to produce a biofilm • Biofilms may disperse and seed new sites of infection Adherence 3 Vibrio cholerae adhering to brush border of rabbit villi Escherichia coli adhering to brush border of calf villi via a capsule Adherence 4 Staphylococcus aureus Gram-positive biofilm cocci in chronic wound Adherence: Adhesins and Receptors • Adhesins include: Fimbriae & pili Capsules & slime layers Flagella (in some species) (lipo)teichoic acids (Gram-positives) • Host receptors include: Blood group antigens Extracellular matrix proteins e.g fibronectin, collagen Barriers to colonisation or infection Eyes: Lysozyme dissolves cell walls Normal flora competes with pathogen Mucus in lungs & trachea prevent colonisation Skin: physical barrier produces antimicrobials normal flora inhibits pathogens Stomach pH inhibits or kills bacteria Normal flora competes with pathogen Flushing of urinary tract prevents colonisation Cilia projecting from the respiratory epithelium in the lungs Steps in infectious disease 3 Reservoir Transport to host Tissue damage Adherence & Colonisation Invasion of tissues Evasion of host defense Invasion • Some bacteria are able to penetrate into, through or between cells = invasion of host cells & tissues • Some bacteria can invade epithelial cells e.g. Shigella • Others invade phagocytic cells e.g. Salmonella, Mycobacteria, Legionella Epithelial cells Invasion using lytic compounds • Often accomplished by lytic compounds that attack the host tissue • Examples: collagenase, phospholipases, haemolysins • Invasiveness also determined by evasion of host defences • e.g. Streptococcus pneumoniae INVASINS = VIRULENCE FACTORS Steps in infectious disease 4 Reservoir Transport to host Tissue damage Adherence & Colonisation Invasion of tissues Evasion of host defence Host defences • The immune system is very efficient at eliminating non-pathogenic bacteria • Macrophages and other phagocytes: engulf and kill bacteria • Cytotoxic cells: kill cells infected with bacteria Image of a macrophage engulfing bacteria Bacterial avoidance of phagocytosis Resisting phagocytosis: bacteria produce structures preventing effective contact: capsules, special surface proteins Survival inside phagocytic cells: often by very pathogenic bacteria: they can escape one of the most effective defences Host defences -antibodies • B cells produce antibodies. Different roles: Microbe Prevent attachment Microbe Microbe Phagocyte Help phagocytosis (act as opsonins) Microbe Microbe Clump microbes Toxin Microbe Neutralise toxins Attracts complement system Microbe Avoidance Antibody avoidance • Capsules (sometimes not immunogenic because they resemble host structures) • Antigenic variation: bacteria can switch between different types of a surface structure • E.g. : Streptococcus pneumoniae can make > 50 capsule variants • Sometimes degradation of antibodies Avoidance of complement • Capsules can prevent complement activation • Lipopolysaccharides (Gram-negatives) sometimes hinder pore formation Steps in infectious disease 5 Reservoir Transport to host Tissue damage Adherence & Colonisation Invasion of tissues Evasion of host defense Tissue damage Tissue damage may occur in several ways: 1. Iron acquisition 2. Direct effects of bacterial toxins 3. Indirect effects of bacterial toxins 4. Induction of autoimmune responses TOXINS = VIRULENCE FACTORS Nutrient Acquisition Iron (Fe) uptake Iron is an essential element for bacterial growth Tissues: free iron levels are below that required to support bacterial growth To acquire enough iron to grow, bacteria express high affinity iron uptake systems 1. Siderophores: bind iron with high affinity Bacterial Toxins Two types: 1.Exotoxins – act on specific targets (e.g. protein synthesis) 2. Endotoxin (LPS): bound to cell – action is indirect: activates many host systems that cause damage Comparing Exo- & Endotoxins Exotoxins Endotoxin Made by Gram + and -ve Protein Secreted by living bacteria Made by Gram -ve Lipopolysaccharide Part of cell membrane, released on cell lysis Usually heat labile Usually heat stable Highly immunogenic Weakly immunogenic Potentially lethal Lethal at higher concentrations Exotoxins Human exposure to exotoxin can occur in different ways • Ingestion of preformed exotoxin Example: food poisoning by Staphylococcus aureus - cannot colonise the gut, but toxin in food causes poisoning • Colonisation of mucosal surface or tissue followed by toxin production Example: Vibrio cholerae, cause of cholera - colonises the gut but does not invade, cholera toxins leads leads hypersecretion of water and chloride ions and dehydration • Colonisation of wound followed by toxin Exotoxins – more examples • Tetanus toxin – a neurotoxin, interferes with synapse function • Diphtheria toxin - inhibits mammalian protein synthesis – Diphtheria has mortality of up to 20% in very young/very old. Many other products e.g proteases, lipases, haemolysins may have toxic effects on mammalian cells Endotoxin Structure of LPS • Called endotoxin because it is bound to cells, released when bacterium lyses, or during cell growth • Lipid A part can have endotoxin activity • Activates many host systems that cause damage, leading to fever; shock; blood coagulation; inflammation. • Important for Gram negative pathogens like Steps in infectious disease 6: Exit Reservoir Transport to host Tissue damage Adherence & Colonisation Invasion of tissues Evasion of host defense Exit routes -for continued life of the pathogen Mostly passive escape: faeces, urine, saliva, etc. Prokaryotes are not ‘primitive’ organisms highly evolved though 3.5 billion years Their simplicity and adaptability is part of their beauty! Basically….. If you don’t like bacteria then you are on the wrong planet! Stewart Brand (1960’s environmentalist) Prokaryotes in summary 1 • Structure and functional adaptations contribute to success – Circular chromosome with plasmids – Fimbria adhesion, pili conjugation, flagella motility – Capsule adhesion/evasion – No nucleus or membrane enclosed organelles Fimbriae Cell wall Circular chromosome Capsule Sex pilus Internal organization Flagella Prokaryotes in summary 2 Rapid reproduction and mutation and genetic recombination gives success – Short doubling time- binary fission Nutritional and metabolic adaptations Benefit or harm; mutualist, commensal, pathogen