FFP1ML4 Pathogenesis of Bacterial Infection 2023 PDF

Leading the world to better health  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Session ID: FFP1ML4 Pathogenes...

Leading the world to better health  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Session ID: FFP1ML4 Pathogenesis of Bacterial Infection Class Year 1 Course Undergraduate Medicine Lecturer: Aoife Kearney Prof Manaf AlQahtani Date 22nd October 2022  LEARNING OUTCOMES 1. Differentiate the normal flora (microbiome) from virulent & opportunistic pathogens 2. Explain how pathogens are transmitted 3. Describe how pathogens gain entry into the body and cells 4. Explain how pathogens avoid being killed by the immune system 5. Describe how pathogens spread in the body 6. Differentiate between endotoxins and exotoxins 7. Discuss host risk factors for infection  PATHOGENESIS the mechanisms involved in production of disease  OR RATHER….. How can something so small cause so much trouble? Image source: https://en.wikipedia.org/wiki/Staphylococcus_aureus // Dermentnz.org  DEFINITIONS Pathogen: a microorganism that is able to cause disease (pathology) Pathogenicity: the ability to produce disease in a host Virulence: the capacity/severity of a microorganism to cause disease or to invade  PATHOGENICITY VS VIRULENCE Image source:https://www.youtube.com/watch?v=jieJklfNnM4  LEARNING OUTCOME 1. Differentiate the normal flora (microbiome) from virulent & opportunistic pathogens  WHAT PERCENTAGE OF BACTERIA CAN CAUSE DISEASE IN HUMANS? A. < 1% B. 5% C. 10% D. 25% Source: https://microbiologysociety.org/why-microbiology-matters/what-is- microbiology/microbes-and-the-human-body/microbes-and-disease.html Image source: https://link.springer.com/chapter/10.1007/978-981-10-7684-8_1 Image source: https://theconversation.com/the-human-microbiome-is-a-treasure-trove-waiting-to-be-unlocked-118757  NORMAL FLORA (MICROBIOME) GOOD BUGS / COMMENSALS / MICROBIOTA In or on our bodies without causing disease Mostly non – pathogenic (Do not cause disease) Can cause infection if Escape from their usual location Barrier is breached Host is immunosuppressed More on the microbiome in ‘Classification of Microbes and The Microbiome and Health’  VIRULENT BACTERIA Virulent bacteria Increased ability to invade or damage the host Primary pathogens Able to cause disease as a result of their presence within the host Can live among normal flora without causing disease in host “Colonized” Virulence factors Genetic/biochemical/structural features of a pathogen that enable it / enhance its ability to produce disease  METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) colonisation infection  OPPORTUNISTIC BACTERIA Low intrinsic virulence Usually don’t cause infections in non immuno- compromised patients May cause serious infections in certain circumstances Immunocompromised foreign body More on opportunistic bacteria in ‘Introduction to opportunistic infection’ WHY DOES INFECTION OCCUR? The The state organis of the m is host virulen t The Surviva size of l in the the host inoculu m The portal of entry  LEARNING OUTCOME 2. Explain how pathogens are transmitted FROM THE PATHOGEN’S PERSPECTIVE Get in – Portal of Entry Get out and Attach to spread cells further Defeat/ Cause evade the damage to immune host cells system  Get in – Portal of Entry Get out and Attach to spread cells further Cause Defeat/evade damage to the immune host cells system  PORTALS OF ENTRY 1. Ingestion – Salmonella food poisoning 2. Inhalation - Tuberculosis 3. Penetration - HIV 4. Sexual - Chlamydia 5. Vertical - Group B Streptococcus  LEARNING OUTCOME 3. Describe how pathogens gain entry into the body and cells 4. Explain how pathogens avoid being killed by the immune system  Get in – Portal of Entry Get out and Attach to spread cells further Defeat/ Cause evade the damage to immune host cells system  ADHESION Adhesion of the bacteria to host cells is required Establishes a stable population of bacteria within the host Prevents bacterial clearance from mechanical host defences Adhesion occurs through receptor / ligand mediated processes (Adhesins) Small bacterial protein ligands which recognise specific receptors on host cells  INVASION To facilitate invasion pathogens can employ biochemical virulence factors called “Invasins” Invasins Proteins Damage host cells and facilitate spread and invasion Hylauronidase, Kinase, Collagenase  Get in – Portal of Entry Get out and Attach to spread cells further Defeat/ Cause evade the damage to immune host cells system  IMMUNE EVASION Presence of bacteria in the host induces immune responses to attempt bacterial eradication To ensure ongoing survival bacteria have developed numerous mechanisms to prevent immune mediated clearance Inhibition of phagocytosis Survival within phagocytes Immune cell destruction  INHIBITION OF PHAGOCYTOSIS Capsule Composed of polysaccharides which sits outside the cell membrane Pathogens associated with meningitis and pneumonia (Neisseria meningitides, Streptococcus pneumonia, Haemophilus influenza)  INHIBITION OF PHAGOCYTOSIS Source: https://courses.lumenlearning.com/microbiology/chapter/virulence-factors-of-bacterial-and-viral- pathogens/  SURVIVAL WITHIN PHAGOCYTES Escape the phagosome Listeria monocytogenes Prevent phagosome / lysozyme fusion Mycobacterium tuberculosis Survival within phagolysosome Staphylococcus aureus  IMMUNE CELL DESTRUCTION / EVASION Some bacteria are also able to produce enzymes that directly target immune cells or prevent their function Leucocidins Pore forming enzymes which target phagocytes (Panton – Valentin Leucocidin of Staphylococcus aureus) Streptolysin Pore forming enzyme produced by Streptococci Coagulase Produced by S. aureus, converts fibrinogen to fibrin which promotes clotting, coats bacteria in fibrin which acts as barrier to immune cells  CAUSE DAMAGE TO HOST CELLS Bacterial enzymes damage host cells as well as being important in immune evasion Invasins Toxins Superantigens  Get in – Portal of Entry Get out and Attach to spread cells further Defeat/ Cause evade the damage to immune host cells system  LEARNING OUTCOME 6. Differentiate between endotoxins and exotoxins  BACTERIAL TOXINS – 2 TYPES Toxins are compounds / chemicals which are toxic to host cells by directly harming host tissue or by interacting with immune cells 1. Endotoxin 2. Exotoxins  ENDOTOXIN Integral part of bacterial cell envelope Release from bacterial cell due to cell lysis or turnover LPS (Lipopolysaccharide) is prototypical example – Gram negative bacteria Can induce pro-inflammatory cascade leading to septic shock Image source: https://open.oregonstate.education/generalmicrobiology/chapter/bacteria-cell-walls/  EXOTOXINS Polypeptide molecules produced by living, mostly Gram-positive bacteria Secreted / released during cell lysis, bacterial replication or by certain antibiotic use (β-lactam antibiotics) Many target specific cells to induce toxic effects and can act locally or distally Cytotoxins Neurotoxins Enterotoxins  SUPERANTIGENS Type of exotoxin Initially discovered in strains of Staph aureus (TSST- 1) Superantigens cause hyperactivation of the immune system mediated via interaction of MHC Class II on T cells Non specific binding at these sites cause polyclonal expansion of T cells leading to a shock syndrome  EXOTOXINS VS ENDOTOXINS Features Endotoxin Exotoxin Source Gram negative Gram positive >> bacteria Gram negative bacteria Chemical Lipopolysaccharide Polypetides or Composition s or proteins lipooligosaccharid es Mechanism of Released on Secreted by Release bacterial cell lysis bacteria >>> released on bacterial cell lysis Examples Meningococcal or Cholera, Tetanus, other Gram Botulism negative sepsis  LEARNING OUTCOME 5. Describe how pathogens spread in the body  DISSEMINATION – HOW PATHOGENS SPREAD IN THE BODY 1. Spread through tissues or tissue planes 2. Haematogenous 3. Lymphatic 4. Carriage within macrophages 5. Ascending/descending spread within a tract  Get in – Portal of Entry Get out and Attach to spread cells further Cause Defeat/evade damage to the immune host cells system  HOW ARE PATHOGENS TRANSMITTED? 1. Person-to-person by direct contact: skin carriage 2. Respiratory: coughing, sneezing 3. Gastrointestinal: diarrhoea 4. Sexually: genital discharge /ulcer 5. Vertically & Perinatally  LEARNING OUTCOME 7. Discuss host risk factors for infection  HOST FACTORS Certain factors will increase the susceptibility of the host to infection Increase the likelihood of severe manifestations of infection WHAT MAKES A PERSON MORE SUSCEPTIBLE TO INFECTION?  HOST FACTORS Extremes of age Diabetes Immunosuppression – Disease induced: cancer / asplenism / HIV/ renal failure / hepatic failure – Medications: chemotherapy, steroids, other immunosuppressive medications  HOST FACTORS Major breach in skin/mucosa – Recent major surgery Prosthetic material – IV lines – Urinary catheters – Ventilation – Prosthetic joints Anatomical abnormality or malfunction – Complications post surgery Antibiotic therapy – Clostridium difficile infections post antibiotics  SUMMARY Bacteria can form part of the normal flora (microbiome), cause opportunistic infection in cases of host compromise or have an increased ability to invade or cause disease (virulent) Virulent bacteria can colonize the host as well as cause disease as a result of their presence within the host (primary pathogens) Bacteria utilize multiple portals of entry and mechanisms of transmission as part of their pathogenesis cycle Adhesins and invasins facilitate bacterial attachment and entry into the host Immune evasion of bacteria is facilitated by a number of mechanisms included inhibition of phagocytosis, survival within and destruction of immune cells Exotoxins and endotoxins are the two types of bacterial chemicals which cause host cell toxicity either through direct damage or immune cell dysregulation There are a number of risk factors that make a person more susceptible to infection Thank you