Week 11 - Microbial mechanisms of pathogenicity Sections 1 QM+.pptx

MD117 – The Microbial World & Huma Microbial Mechanisms of Pathogenicity Section 1 Part 1 Dr. Olivier Marchès Learning objectives: Section 1 part 1 • Describe how microorganisms enter a host and portals of entry • How to quantify pathogenicity: Infectious dose and lethal dose. Definitions • P...

MD117 – The Microbial World & Huma Microbial Mechanisms of Pathogenicity Section 1 Part 1 Dr. Olivier Marchès Learning objectives: Section 1 part 1 • Describe how microorganisms enter a host and portals of entry • How to quantify pathogenicity: Infectious dose and lethal dose. Definitions • Pathogenicity – the ability to cause disease • Virulence – the degree of pathogenicity • Virulence is not an absolute measure. All infections result from host-pathogen interaction and require a susceptible host Stages for a successful pathogen • Transmission: pathogen leave the reservoir and enter the host via portal of entry • Evasion of primary host defenses • Adherence: pathogen adhere to the surface of the host • Invasion: pathogen invade the body of the host • Multiplication: pathogen can grow and multiply • Damage to the host (toxins) while resisting host defenses • Exit the body and return to reservoir or new host Portal of entry Portals of entry • Respiratory tract ear nose and throat • Gastrointestinal tract • Genitourinary tract • Direct break through skin trauma/cuts or surgery • Parenteral route direct into blood and / or tissues Respiratory tract • Entry point for pathogens causing common diseases e.g. • Common cold (Viruses (Rhinovirus)) • Flu (Influenza virus) • Pneumonia (eg: Strep. pneumoniae) • Tuberculosis (Mycobacterium tuberculosis) Gastrointestinal tract • Ingestion of food or water containing pathogen • Faecal oral route – most microbes destroyed by stomach acid and enzymes but some survive and can infect Examples: • Gastroenteritis • Campylobacter • Salmonella enterica and Salmonella typhi (Typhoid fever) • Some types of E.coli • Dysentery • Shigella • Cholera • Vibrio cholerae • Hepatitis A (HAV); contamination food borne, person to person Genitourinary tract • Sexually transmitted • Neisseria gonorrhoeae - gonorrhoea • Treponema pallidum – syphilis • Herpes simplex virus – Herpes infections • Non sexually transmitted • urinary tract infections – E. coli and others • Candida infections (thrush) Skin • Largest organ of body and important defence against disease • Unbroken skin is impenetrable to most microorganisms but some can gain access via hair follicles and sweat gland ducts • Hookworm larvae can bore through intact skin (rash); some fungi grow on keratin in skin Parenteral route • Some pathogens gain access to the body when the mucosal or skin barriers are penetrated or injured. This route of entry is called Parenteral route • Skin breached by: • Traumatic injury/ cuts • Bites – animal and human • Contaminated needles • Blood transfusion Examples  HIV  Hepatitis B  Gas gangrene – Clostridium perfringens  Tetanus – Clostridium tetani Routes of transmission • Air • e.g. droplets via sneezing • Food or water • Gastroenteritis • Direct or indirect contact • Hands • Door handle • Vectors • Insect bites • Medical instruments (fomites) How to measure pathogenicity • Infectious dose • Lethal dose Infectious dose: ID50 • The number of cells of a microorganism required to cause disease varies between pathogens • Salmonella >100.000 • Campylobacter ~ 500 to 10.000 • Shigella <10 • Virulence can be expressed as the ID50 - infectious dose for 50 % of the test population • not an absolute value • used to compare relative virulence under experimental conditions Infectious dose • Can differ for same organism at different portals of entry Bacillus anthracis endospores - Anthrax Portal of Entry Skin ID50 10–50 endospores Inhalation 10,000–20,000 endospores Ingestion 250,000–1,000,000 endospores Lethal dose: LD50 A graph like this is used to determine LD50 by plotting pathogen concentration against the percent of infected test animals that have died. In this example, the LD 50 = 104 pathogenic particles. Learning objectives: Section 1 part 2 • Describe microbial adherence to host cells • Describe biofilms Adherence • On mucous membranes particularly, pathogens have to adhere to tissue surface • Tissue is covered in protective layer, e.g. mucus • Pathogens needs specific mechanism to be able to adhere to cells Adherence - adhesion Pathogen produces surface molecules called adhesins, often on fimbriae / pili, which bind specifically to receptors on cell surface Adherence Majority of adhesins are glycoproteins or lipoproteins and bind sugar residues on host cells Bacteria (purple) adhering to human skin E. coli adhering on human urinary bladder cells Pathogen modification of cell surface • Pathogen may alter cell surface to enable it to adhere • e.g. some E. coli inject a protein directly into cells which serves then as receptor for the bacteria Biofilms Multi-species communities forming on a surface, normally at a liquid / air interface Could cause up to 65% of human infections e.g. dental plaque Examples of biofilm-associated infections Contact lens keratitis Prosthetic heart valve endocarditis Catheter infection Diabetic foot infection Advantages of biofilm lifestyle for bacteria • Protection from host defences • Antibiotic resistance - bacteria growing in biofilms are intrinsically less sensitive to antibiotics than bacteria living planktonically (free in suspension) - reasons unclear but not just due to need for antibiotic to penetrate biofilm – bacteria exhibit different characteristics when growing as biofilm