Virulence Factors DTH23 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 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 cause disease in an otherwise healthy individual Opportunistic pathogen: always a member of the normal microbiota and only causes disease in an immunocompromised host. Pathogenicity: the ability of the pathogen to cause disease 4 Terminology Virulence: degree or intensity of pathogenicity Virulence factors: mechanisms that determine the degree to which the pathogen causes damage, invasion and infectivity 6  Chain of infection Virulence Agent Dose Exposure Susceptibility 7  Review microbiology Molecular Koch’s postulates sessions Image credit: lumenlearning.com 8 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 elements 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 Image Credit: Alila Medical Media / Shutterstock 11 Pathogen entry, adhesion and colonisation Refer to Immunology sessions Image credit: www.differencebetween.com 12 Adhesion  Pili Fimbriae Capsules Bacterial cell walls Image credit: bio.libretexts.org Video: Mechanism of Bacterial Adhesion in Stap hylococcal Infection Revealedwith Atomic detail Image Credit: Pearson Education inc. 14  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  Adhesins 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 Image credit: Wikipedia.com Images credit: bio.libretexts.org 16 Bacterial adhesin examples and host sites Pathogen Disease Adhesin Attachment Site Streptococcus Strep throat Protein F pyogenes Streptococcus mutans Dental caries Adhesin P1 Neisseria Gonorrhea Type IV pili gonorrhoeae Enterotoxigenic Traveler’s Type 1 fimbriae E. coli (ETEC) diarrhea N- Vibrio cholerae Cholera methylphenylalanine pili 17 Bacterial adhesin examples and host sites Pathogen Disease Adhesin Attachment 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 fimbriae Intestinal E. coli (ETEC) diarrhoea epithelial cells N- Vibrio cholerae Cholera methylphenylalanine Intestinal pili epithelial cells 18  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: 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 protective coat which deters killing mechanisms when phagocytosed 20 Exoenzymes and Toxins as Virulence Factors Pathogen entry, adhesion and colonisation Image credit: www.differencebetween.com 22 Exoenzymes Extracellular enzymes: enzymes secreted by cells which function outside of those cells Invade host cells, deeper tissues specific to particular tissue structure: enables invasion/supports own growth/defends against immune system Image credit: lumenlearning.com 23 Exoenzyme class examples: 24 Toxins Biological poisons produced by some pathogens Invade and damage tissues Toxigenicity: ability of a pathogen to produce toxins to cause damage to host cells. 2 types: Endotoxins Exotoxins Image credit: Wikimedia Commons 25 Endotoxins Derived from gram-negative bacteria Stimulates general systemic inflammatory response Remains stable at high temperatures. 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 Exotoxins Potent protein molecules produced by wide variety of pathogenic - mainly gram positive bacteria/some gram negative 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. Inactivated by heat (>41°C/106°F) Low concentrations of exotoxin can be lethal Grouped in 3 categories: intracellular targeting, membrane disrupting, superantigens 27 Terminology to describe pathogens in bloodstream Usually end in - aemia Can you name the following conditions? Presence of bacteria in the blood ? Pus-forming bacteria in the blood ? Presence of toxins in the blood ? Multiplying bacteria in the blood ? 28 Terminology to describe pathogens in the bloodstream Usually end in - aemia Can you name the following conditions? Presence of bacteria in the blood Bacteraemia Pus-forming bacteria in the blood Pyaemia Presence of toxins in the blood Toxaemia Multiplying bacteria in the blood Septicaemia 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 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 recognition by the host’s immune response. Can you think of any pathogens where this occurs? 30 Further protection against the immune system: Destruction of phagocytes with production of leukocidins Destruction of T lymphocytes Intracellular position: immune defences not able to reach them Avoid killing methods within the phagocyte 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 Porphyromonas Gingivalis  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 Streptococcus Mutans 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 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 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 Candida Albicans Most common etiological factor of opportunistic human fungal infections. Main virulence factors: Exoenzymes: secreted aspartyl proteases –known as ‘Sap Proteins’ adhesions Pleomorphism- C. albicans responds to changing environmental conditions/adapts to biological niches 37 Adhesins as Virulence Factors in candida albicans 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 additional resources Lumen Learning.com, Virulence Factors of bacterial and viral pathogens (online) Available at: https://courses.lumenlearning.com/microbiology/chapter/virulence-factors-of-bacterial-and- viral-pathogens/ [accessed February 2021] Wikipedia, Virulence factor, (online) Available at: https://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: https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Kaiser)/Unit_3 %3A_Bacterial_Pathogenesis/5%3A_Virulence_Factors_that_Promote_Colonization/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 Dentistry, Periodontal Pathogenesis (online) Available at: https://pocketdentistry.com/5-periodontal-pathogenesis/ [accessed February 2021] 41