Virulence Factors GN PDF

Virulence Factors Biomedical Sciences Ms P Lazarou GDC Learning Outcomes 1.1.3 Explain general and systemic disease and their relevance to oral health 1.1.4 Explain the aetiology and pathogenesis of oral disease 1.1.7 Explain the potential routes of transmission of infectious agents in den...

Virulence Factors Biomedical Sciences Ms P Lazarou GDC Learning Outcomes 1.1.3 Explain general and systemic disease and their relevance to oral health 1.1.4 Explain the aetiology and pathogenesis of oral disease 1.1.7 Explain the potential routes of transmission of infectious agents in dental practice […] Intended Learning Outcomes: - Define the terminology associated with virulence and virulence factors - Recall and list the pathogens which infect the human body - Describe the various mechanisms that pathogens deploy to destroy, cause malfunction of host cells and evade the immune response Terminology Bacteriaas Protozoa fungi · · Pathogen: Any microorganism which is able to cause disease in a host - organism Task: List pathogens which could cause disease in humans Primary pathogen: an environmental microbe that is able to- healthy host cause disease in an otherwise healthy individual Opportunistic pathogen: always a member of the normal - Immuno microbiota and only causes disease in an immunocompromised compromised host. host. Pathogenicity: the ability of the pathogen to cause disease 4 Terminology cause serious than others to Virulence: Some more likely diseasese - degree or intensity of pathogenicity Virulence factors: - mechanisms that determine the - degree to which the pathogen causes damage, invasion and infectivity factors that helps microorganism to invade avoid host defenses 6. ,  more susceptible weakened immune system Chain of infection - Virulence Agent Degree of Dose Intensity of Identity agent to cute How much disease causes disease ? Exposure Susceptibility of host to agent How did it - get there ? Diabetes ? Immunosuppred ? 7  Prove Causative relationship between microorganism and disease. Review microbiology Molecular Koch’s postulates sessions factors) Identify encoded L (virulence genes of > - Extract + grow micro organisms microorganism in virulence factor. pure culture. - Introducemicroorganism healthy most to causes disease & > - > - microorganism extracted Identify again from rectly model microorganism -Microorganism should be causing disease Image credit: lumenlearning.com same as original. 8  · virulence factors are trying to compete with defense factors. Process of infection Virulence factors allow a - - pathogen to outcompete host cells and resist their defences To survive, they require: a suitable environment a source of nutrients protection from harmful S elements Establish within body. Image credit MacGraw-Hill Companies. Sourced from: wikipedia.org 9 Virulence factor mechanisms Adhesion Evasion of phagocytosis (antiphagocytic factors) Immunoevasion Immunosuppression Toxigenicity: exotoxins and endotoxins Enzymatic: exoenzymes 10 Imicroorganism. a several mechanisms Image Credit: Alila Medical Media / Shutterstock 11  Pathogen entry, adhesion and colonisation oral cavity enters though. Refer to common cold & Immunology - Sticks sessions · Adhesions ↑ Protein or ↳ virulence Glycoprotein factor I attach to receptors on Pathogenicity host all ↳ ability of pathogen to attach to host tissue e. Image credit: www.differencebetween.com 12 Adhesion  How does adhesion happen? ↳ Bind to Pili receptor Fimbriae thread like protein adhesion molecules > - siteson bacteria surface on. host all Capsules forcefield around bacterium > -. surface. Bacterial cell walls Image credit: bio.libretexts.org /mucosal , urinary Video: Mechanism of Bacterial Adhesion in Stap hylococcal Infection Revealedwith Atomic detail Image Credit: Pearson Education inc. 14  retract moverextend + - Using pili to adhere to host cells Class IV pili have a ‘twitching’ motility Found at poles of bacilli Enables ‘gliding’ motion along solid host cell surface Pili retract and extend, allowing movement Bacterium can ‘slingshot’ over the cellular surface Images credit: bio.libretexts.org 15 Oral significance aureus(bacteria) e uses protein to A host /Staphylococcus C as adhesion. Adhesins Angular prevents phagocytosis engulf large particle) Chiliti Cell walls of bacteria contain surface proteins/glycoprotein called adhesins: bind to targeted receptor molecules on host cell surface allows the bacteria to adhere closely to host cell thereby resisting physical removal and allowing colonization Many bacteria use one or more adhesins to colonise host cells Steptococcuspyogenes a lympathic - proteinfe Image credit: Wikipedia.com Images credit: bio.libretexts.org 16 I or more to alter adhesive tips. /colonise-bacteria can and invade immune defenses host · enter receptor cells cells physical removal, ↓ adheres , resists allows for colonization. Bacterial adhesin examples and host sites Pathogen Disease Adhesin A.achment Site Streptococcus Respiratory Strep throat Protein F pyogenes epithelial cells Streptococcus mutans Dental caries Adhesin P1 Teeth Neisseria Gonorrhoea Type IV pili Urethral gonorrhoeae epithelial cells Enterotoxigenic Traveller's Type 1 Fmbriae IntesHnal E. coli (ETEC) diarrhoea epithelial cells N- Vibrio cholerae Cholera methylphenylalanine IntesHnal pili epithelial cells 18  bacteria being engulfed -Stops Capsules Some bacteria produce capsules Aid in adhesion Act to help in immune evasion- prevent phagocytosis by cells of the immune system Capsule composition prevents adhesion of antibodies Capsule size deters phagocytosis 19 Fimbraie and Cell walls Some pathogens produce virulence factors that enable evasion of the immune system: acid mycolic. Fimbriae of some Streptococcus species contains M protein- this alters the surface of the bacterium which inhibits phagocytosis Mycolic acid (waxy substance) is produced in it’s cell wall by Mycobacterium tuberculosis. Acts as a protec?ve coat which deters killing mechanisms when phagocytosed 20  Extracellular enzymes / secreted by cell , functions outside of. cell Exoenzymes and Toxins as Virulence Factors Pathogen entry, adhesion and colonisation Image credit: www.differencebetween.com 22  break down of Structures Exoenzymes ↳ cause disease. Extracellular enzymes: enzymes Start secreted by cells which function process outside of those cells invasion Invade host cells, deeper tissues enzyme of that breaks specific to particular tissue > down structure: enables protein. invasion/supports own growth/defends against immune Hyaluronan) system Image credit: lumenlearning.com 23 Exoenzyme class examples: u ( further colonization. 24 Toxins Biological poisons produced by - some pathogens Imicroorganisms Invade and damage tissues Toxigenicity: ability of a pathogen to produce toxins to cause damage to host cells. More toxic , more damage. 2 types: Endotoxins Image credit: Wikimedia Commons Exotoxins 25  response. immune systems inflammatory lipopolysaccharide (CPS) trigger -agrumneuereleasendotoxinsenwhenena - l Endotoxins periodontal disease (subgingival) Derived from gram-negative bacteria - Stimulates - general systemic inflammatory response Remains stable at high temperatures. very stable + strong ! Requires heating at 121°C (250°F) for 45 minutes to inactivate If endotoxin concentration is low: host’s inflammatory response against infection is effective If endotoxin concentration in the blood is high: causes severe drop in blood pressure, multi-organ failure and possibly death. 26  can be used to treat : ms Individual muscle spasms Exotoxins Potent protein molecules produced by wide variety of pathogenic - mainly gram posi?ve bacteria/some gram nega?ve bacteria Specific in their action and the cells they interact with Each exotoxin targets specific receptors on specific cells- damages those cells through individual molecular mechanisms. Inac?vated by heat (>41°C/106°F) Low concentra?ons of exotoxin can be lethal Grouped in 3 categories: intracellular targeHng, membrane disrupHng, superanHgens 27  Terminology to describe pathogens in the bloodstream Usually end in - aemia Can you name the following condiHons? Presence of bacteria in the blood Bacteraemia ? abscesses Pus-forming bacteria in the blood Pyaemia Presence of toxins in the blood Toxaemia Multiplying bacteria in the blood Septicaemia Septic esnock ! 29 Virulence factors promoting infection Further protection against the immune system: Production of exoenzyme coagulase by staphylococcus aureus: triggers fibrinogen-to-fibrin cascade enabling bacteria to be coated by fibrin clots- prevents phagocytosis - > body can't getrid of it. Production of kinases stimulate digestion of fibrin clots: depending on conditions –pathogen needs to escape and spread from clot. Antigenic variation: surface proteins are altered to avoid Antibodies and not recognition by the host’s immune response. Can you think of any pathogens where this occurs?Darients/strains) recognized due to variation. 30  Further protection against the immune system: secreted by various - Destruction of phagocytes with production of leukocidins Streptococcus bacteria Destruction of T lymphocytes. white blood - cells If destroyed level virues Intracellular position: immune defences not able to reach & of host them immunosipression > - virulence factors - within. e- Avoid killing methods within the phagocyte cu be total. Video: How Pathogens Evade the Immune System - YouTube 31 Viral virulence Adhesins- mediated by adhesins that are part of viral capsid or membrane envelope. Interact with specific cell receptors (tropism). E.g spike protein hemagglutinin on influenza virus; glycoprotein g20 found on HIV Antigenic variation found to occur in some enveloped viruses: antigenic drift: result of point mutations causing minor changes in the spike proteins antigenic shift: gene re-assortment results in major changes in spike proteins 32 Virulence factors in oral health  negative or gram positive?? Bacteria gram Porphyromonas Gingivalis (P Gingivalis). breakdown e --tissue fimbriae modify and stimulate  immune responses such as cytokine - secretion or cytokine inhibition in the periodontium - Gingipains (proteases-exoenzyme)  produced by p.gingivalis which break down structural proteins of periodontium e.g collagen, elastin, - fibronectin - Image credit: researchgate.net 34  carries tooth Streptococcus Mutans Tooth decay Main VF associated with cariogenicity: Adhesion, acidogenicity and acid tolerance. These factors work together to change the ecology of dental plaque. Higher numbers of S mutans as well as other acid producing and acid tolerant bacterial species Live in biofilm and convert sugar and starch into acid. The pH drops quickly due to the increase in cariogenic bacteria when the available carbohydrate is being fermented Susceptibility to enamel demineralization increases at this time of bacterial proliferation and volume of acid being produced. 35  Herpesabian. Herpes simplex virus Hides from the immune system in neurons and non-neuronal cells- may persist for many years. Emerges as pathogenic form when immune resistance is low. Presents clinically as herpes labialis (cold sore) 36  pathogenic yeast around munosuppressed becomes - when in can carry pathogenic I Candida Albicans Hu find in biofilms. Most common etiological factor of can be found on dentures opportunistic human fungal infections. Main virulence factors: breakdown proteins ↑ Exoenzymes: secreted aspartyl proteases –known as ‘Sap Proteins’ adhesions Pleomorphism- C. albicans responds to changing environmental conditions/adapts filament forming biom to biological niches extracellular enzymes cause infection produces hydrolytic - tissue invasion. 37 Adhesins as Virulence Factors in candida albicans change I adapt invade colonize Image credit: trends in microbiology 38 Conclusion Pathogens have and continue to evolve strategies through virulence factors to increase virulence and avoid immune responses. The constant interaction between the pathogen and host cells is a dynamic one, where the production of new virulence factors are countered by the host. Increase of cytotoxic T cells in the host enables the pathogens to produce ‘escape mutations’ in order to avoid being a future target. Therefore: pathogens will continue to evolve and emerge. The most successful ones being those which take advantage of the host without causing death. 39 References and addiHonal resources Lumen Learning.com, Virulence Factors of bacterial and viral pathogens (online) Available at: hTps://courses.lumenlearning.com/microbiology/chapter/virulence-factors-of-bacterial-and- viral-pathogens/ [accessed February 2021] Wikipedia, Virulence factor, (online) Available at: hTps://en.wikipedia.org/wiki/Virulence_factor [accessed February 2021] Biology Libretexts.org, (2021) The ability to adhere to Host cells and Resist removal (online) Available at: hTps://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Kaiser)/Unit_3 %3A_Bacterial_Pathogenesis/5%3A_Virulence_Factors_that_Promote_Coloniza?on/5.2%3A_T he_Ability_to_Adhere_to_Host_Cells_and_Resist_Physical_Removal [accessed February 2021] 40 Further reading: McMahon R, Sloan P. (2000). Essentials of Pathology for dentistry. London: Harcourt Publishers Limited. Pocket Den?stry, Periodontal Pathogenesis (online) Available at: hTps://pocketden?stry.com/5-periodontal-pathogenesis/ [accessed February 2021] 41