Bacterial Pathogenicity PDF

BACTERIAL PATHOGENESIS Dr Lorina Badger-Emeka COM-KFU  Intended Learning Outcomes Students should be able to: 1. know the important steps in bacterial virulence 2. know the role of colonization, adherence and invasion in bacteria pathogenesis 3. differentiate between...

BACTERIAL PATHOGENESIS Dr Lorina Badger-Emeka COM-KFU  Intended Learning Outcomes Students should be able to: 1. know the important steps in bacterial virulence 2. know the role of colonization, adherence and invasion in bacteria pathogenesis 3. differentiate between endo and exo toxins 4. know the principles of immunopathogenesis 5. Know how super-antigens work  Introduction Bacterial have the ability to invade an environment, Adhere, colonize, Gain access to food (degradative enzymes) evading host immune They try to create a niche or a colony for themselves Result? by-products (acids, gas, etc.) are produce; leading to damage and harm to the host Mechanisms of Bacterial Pathogenicity Two broad qualities of pathogenic bacteria by which they cause disease: 1. Invasiveness: the ability to invade tissues. It includes mechanisms for colonization (adherence and initial multiplication), production of extracellular substances which facilitate invasion (invasins) and ability to bypass or overcome host defence mechanisms. 2. Toxigenesis is the ability to produce toxins. Exposure to a pathogen Adherence to the site. Invasion Skin or Mucosal membrane TOXICITY: toxins effects are local or systemic Colonisation and growth With the production of Tissue damage: Disease virulence factors INVASIVENESS: further multiplication at original site and distant sites  What is Bacterial Pathogenesis Bacterial pathogenesis is the process through which bacteria cause disease. The degree to which disease is caused is called Virulence OR pathogenicity. The genetic traits by which they cause damage to the human host are known as the virulence factors Bacterial Virulence Bacteria by-products such as gas and acids are traits that lead to virulence Others cause disease by direct tissue damage Or through the release of toxins which are transported by the blood to organs of the body where they effect pathogenesis Virulence involves invasiveness and toxigenecity https://www.slideshare.net/MeherRizvi/mechanism-of- bacterial-pathogenesis-and-virulence  Question 1. Elements of bacterial genome essential for invasion, dissemination, pathogenicity is referred to as: a. Virulence factor of bacteria b. The quorum sensing by bacteria c. DNA bacterial dissemination Summary Bacteria Virulence  Causing a disease To cause a disease, a pathogen must first Gain access to a host, Adhere to host tissue, Penetrate, Evade host defence mechanism, Damage the host either directly or through the accumulation of microbial waste. They must have a preferred point of entry Sites of Bacterial entry into human body MURRAY  Question 2 Which part of the infection cycle involves microbes entering host cells? Port of entry Penetration Binding Answer, B. Penetration  Natural openings in the skin Mucus and epithelia cells that line the upper respiratory tract, the lysozyme and other antibacterial secretions in tears and mucus; The acid and bile in the GI tract All provide protected defences.  Bacteria Factor: Bacterial inoculum Size The bacterial strain, the size of the inoculum are important in causing a disease. Less than 200 needed to cause Shigellosis (Shigella) While 108 inoculum is needed for Vibrio cholera or Campylobacter.  Bacteria factor (Species) Many bacteria are unaffected or have the means to evade host defences. E.g. The outer membrane of gram negative bacteria makes them capable of resisting the action of lysozyme, bile and acid. The Enterobacteriaceae are able to colonise the GI without causing any harm Except when they break out into other regions.  Host factors Host factor also play an important role in bacterial pathogenesis. For example, Congenital defects, Immunodeficiency state Other disease related conditions, will increase a persons susceptibility to infection.  Colonization, Adhesion, and Invasion The next stage of microbial infection is colonisation. It is the establishment of the pathogen at the appropriate portal of entry. Ability to colonise is species dependent. E.g. environmental conditions E.g. Legionella which grow in the lungs does not spread very well at higher temperatures (35°C).  Adherence E. coli and other bacteria have adhesins that help in binding to specific receptors keeping them from being washed away. Certain microbial structures such as glycocalyx and fimbriae (i.e., attachment pili) are involved in adherence.  Microbial adhesions most microbial adhesions are glycoproteins Or lipoproteins located on the glycocalyx, capsule, capsid, pili, fimbriae or flagella  Invasion Invasion of a host aided by the production of bacterial extracellular substances. These substances are referred to as invasins Most are proteins (enzymes). They either destroy the barriers or penetrate into the cells of the barrier. The damage to the host due to this invasive activity becomes part of the pathology of a disease.  Pathogenic actions of Bacteria There are three general mechanism by which bacteria cause damage to the host; 1. Direct damage, tissue destruction 2. Toxin induced damage and 3. Hypersensitivity reactions.  Tissue Damage Google image  Toxin induced damage Toxins are bacterial products that directly harm the tissue or initiate destructive biological activities. They are enzymes Can lead to the lysing of cells The could be categorised as endotoxins or exotoxins  Toxins Types of toxins: Exotoxin and Endotoxin Exotoxin classifications: has the ability to destroy the host membranes Super antigens; have the ability to activate large numbers of T cells leading to shock. A-B component toxins; that have A and B subunits  Exotoxins and Endotoxins Exotoxins Endotoxins Produced by both Gram-positive Produced only by and Gram-negative bacteria Gram-negative bacteria Released from cell Integral part of cell wall Protein Lipid A of lipopolysaccharides Many types of exotoxins Only one type of endotoxin based on structure and function Heat stable Heat liable Diverse range of host cells and systems affected Specific receptors on Diverse range of effects in host target cells host Specific effects on host Toxoids cannot be made Toxoids can be made  Endotoxins Google image They are released when bacteria are killed by phagocytosis or antibiotics. They are NOT tissue or organ specific and can cause general damage (fever, hypotension, weakness) to the host.  Exotoxins There are 5 types of exotoxins, and each are target specific target. Enterotoxins; (entero = intestines) Neurotoxins; (neuro = nerve) Clostridium tetani and C. butulium Cytotoxin; Corynebacterium diphtheria produces a cytotoxin that kills respiratory tract cells Hematologic toxins; include haemolysing and leukocidins that lyse blood cells, and Super antigens.  Super Antigens Super antigens are substances that hyper-stimulate lymphocytes and induce an immune response that is 2000x stronger than normal. – They are toxins Leads to rapid vasodilation and a decrease in blood pressure, resulting in shock. E.g. Staphylococcus aureus and Streptococcus pyogenes produce toxins that can induce toxic shock syndrome. Superantigen courtesy of Murray  Question 3 During a confirmation of a urinary tract infection in a patient, it was ascertained that the infection was as a result of an endotoxin producing bacteria. Which one of the following is the organism? A) Escherichia coli (E. coli). B) Staphylococcus species. C) Streptococcus species. D) Candida albicans Answer?  Immunopathogenesis The host immune response is the principle cause of disease symptoms in patients. The symptoms to a bacterial infection are usually produced by: the innate, immune and inflammatory responses triggered by the infection MECHANISMS FOR ESCAPING HOST DEFENSES courtesy of Murray  Escaping host defences (the capsule) This protective coat makes it difficult for macrophages and neutrophils to digest and break down the microbe Escaping host defences (Anti- phagocytic factors) Google image  Escaping host defences (Masking) Masking: Here microbes produce external components that mimic host cells or makes the microbe invisible to the host immune system. E.g. the M protein of Streptococcus pyogenes mimics the connective tissue of the heart. the immune system accidentally destroys host cell tissues in its attempt to eliminate S. pyogenes.  Summary: Bacterial Virulence Mechanisms Adherence (Colonization) Invasion Degradative enzymes Exotoxins Endotoxin Evasion of phagocytic & immune clearance By products of growth (gas, acid) Superantigens Escaping host defences  References MEDICAL MICROBIOLOGY BY MURRAY ROSENTHAL PFALLER 7TH ED. Chapter 14. pg. 139 8th Ed. Chapter 14, pg. 134 - 142 Images from both Murray and Google.