Bacterial Pathogenesis 2023-2024 PDF

Bacteriele Pathogenese 1 Pathogenese?? 2 Pathogenese?? Ontwikkeling van ziekte Het stapsgewijze ontstaan, ontwikkeling en verloop van een aandoening 3 4 Bacteriele Pathogenese? 5 Bacterie...

Bacteriele Pathogenese 1 Pathogenese?? 2 Pathogenese?? Ontwikkeling van ziekte Het stapsgewijze ontstaan, ontwikkeling en verloop van een aandoening 3 4 Bacteriele Pathogenese? 5 Bacteriele Pathogenese Transmissie van Pathogene bacterie Pathogeen in menselijk lichaam Infectie(ziekte) Ziekteverschijnselen (schade) Gedrag van pathogeen in menselijk lichaam en de veranderingen die het met zich meebrengt in het menselijk lichaam 6 Characteristics of Bacterial Pathogenesis Infectivity = ability of pathogen to establish infection Invasiveness = ability of pathogen to spread to other tissues in body Toxigenicity = ability of pathogen to secrete toxins 7 Definitions related to pathogenesis Definitions and human. (Virulentie factoren) 8 Types of Pathogens  Primary Pathogens ◼ Cause disease upon infection, not normally associated with host  Yersinia pestis, influenza virus  Opportunistic Pathogens ◼ Cause disease under some circumstances, sometimes members of normal flora  Pseudomonas, Candida albicans 9 Virulentie factoren/mechanismen 10 Virulentie factoren 11 Parasitism: Survival of the fittest Host - insusceptible for disease (ongevoelig) – pathogen killed by innate a/o adaptive immunity Host - susceptible for disease (gevoelig) – pathogen survives 12 ◼ Infectie? ◼ Men spreekt over een infectie als een micro-organisme, virus of parasiet in een levend wezen is binnengedrongen en zich daar vermenigvuldigd heeft (dit hoeft niet schadelijk te zijn). ◼ Infectieziekten? ◼ Wanneer het organisme dusdanig veel schade aanricht dat het normaal functioneren van de gastheer is verstoord, spreekt men van een infectie ziekte. ◼ Het micro-organisme wordt bij een infectie die ziekte veroorzaakt (pathogenese) pathogeen of de ziekteverwekker genoemd. 13 Establishing an Infection (Mechanisms of Pathogenesis) 1. Encounter (exposure to portal of entry;confrontatie, blootstelling) 2. Adherence (vasthechting) 3. Colonization (vestigen;nederzetting) – Invasion, multiplication, maintenance 4. Damage to the host (depends on..?) – Toxin production and host “over-reaction” 5. Infect other host (through shedding) 14 mechanismen van bacteriele pathogenese 15 1. Encounter (blootstelling) fecal-oral (cholera) human-human (tuberculosis) animal-human (rabies) vector-borne (plague, Lyme's disease, dengue) environmental contact (anthrax) 16 Porte d’entrée (toegangspoorten) Maagdarmkanaal Luchtwegen Direkt kontakt Placenta 17 18 2. Adherence (Aanhechting) Prevents early clearance (Vibro en E.coli in darmen bij stoelgang, Tb in longen bij hoesten) Often bind host tissues via pili or adhesins (antigens) 19 Diverse adhesie-receptor interacties 20 21  Bacterial adherence to a eukaryotic cell Receptor  specific carbohydrate or peptide residues on the eukaryotic cell surface Adhesin  component of the bacterial cell surface (peptide/carbohydrate) Pilus  hairlike component of the bacterial cell surface (oligomeric pilin protein) Usually interact in a complementary and specific fashion 22 3. Colonization Invasion, multiplication, maintenance Barriers: Competition with normal flora Competition with host for iron Resist: bile, stomach acid, peristalsis, skin secretions, IgA (mucosal antibodies) 23 3. Colonization  Invasion:  Breaching Anatomical Barriers with the aim to find new niche (leefmilieu) with few competitors (e.g. Leptospira)  To gain access to rich nutrient supply 24  How does MO invade in the host? 25 Invasion Invasion mechanisms: – Production invasins – Motility – Avoid host defenses incl. First Line of Defense 26  Invasins proteins (enzymes):spreading factors and factors promoting host cell lysis e.g. collagenase act locally to damage host cells and/or have the immediate effect of facilitating the growth and spread of the pathogen 27 Enzymes that destroy cells (lyses) Act on the human cell membrane by insertion into the membrane – forming a pore that results in cell lysis enzymatic attack on phospholipids – destabilizes the membrane – E.g. Phospholipases produced by Clostridium perfringens 28 Motility and invasion Motile bacteria that can swim chemotactically (flagellen) toward mucosal surfaces may have a better chance to make contact with the mucous membranes, attach, and colonize. Axiale filamenten Vibro cholera 29 4. Damage to host cells Bacteriële Pathogenese van infectieziekten – Host-mediated Pathogenesis – The pathogenesis of many bacterial infections cannot be separated from the host immune response, for much of the tissue damage is caused by the host response rather than by bacterial factors. Classic examples of host response-mediated pathogenesis are seen in diseases such as Gram-negative bacterial sepsis, tuberculosis, and tuberculoid leprosy The tissue damage in these infections is caused by toxic factors released from the lymphocytes, macrophages, and polymorphonuclear neutrophils infiltrating the site of infection Medical Microbiology. 4th edition.Baron S, editor 30  4. Damage to Host : Toxins Poisonous protein substances produced by microorganisms: direct damage or disabling immune system > 220 known bacterial toxins Exotoxins (mostly seen in Gram (+) Bacteria) – secreted outside the bacterial cell Endotoxins – part of the outer cell wall of Gram (-) bacteria Recently: biomedical research for development of novel anticancer drugs and other medicines 31 Exotoxinen: werking Hulp bij verspreiding in weefsel Lysis van cellen (afbraak celmembraan, porievorming) Blokkade eiwitsynthese Invloed chemische reacties (e.g. verhoging cyclisch AMP, blokkade funktie CZS) 32 Invasins vs Exotoxins - 1 Invasins: Exotoxins: Act at a short range Act at remote sites May not kill cells Often cytotoxic (kills cells) More specific and more potent 33  Exotoxins: A + B Subunit Arrangement Many exotoxins that act intracellularly consist of two components subunit A – enzymatic activity subunit B – binds to a specific receptor on the host cell membrane – transfers the enzyme across the membrane 34 Dimeric effect of exotoxins Diphtheria toxin effect A-B chain molecule B-promotes entry EF-2:elongation factor-2 A-inhibitory effect 35 Diphtheria toxin an enzyme that blocks protein synthesis in many cells. Corynebacterium diphteriae: grows mainly in the throat 36 Botulisme toxine (Clostridium botulinum) 37 Tetanus toxin (Clostridium tetani) 38 Tetanospasmin:"spasms" or “Lock Jaw” 39  A-B both blocking effect resulting in inhibition or stimulation 40 Video’s werking botulinum en tetanus toxinen Botulinum toxin for Medical usage - Mechanism of Action – YouTube Tetanus Toxin - YouTube 41 Endotoxins LPS, in OM of Gram negative bacteria – Lipid A is toxic if organisms enter bloodstream Massive immune cell infiltration – Intravenous fluids are screened for Lipid A 42 43 endotoxin Excessive immune response triggered by LPS 44  LPS-binding protein circulating in blood Shock and multiple organ Multi organ system system failure failure 45