Pathogenicity of Bacteria Lecture PDF

Pathogenicity of Bacteria Click to edit Master subtitle style Prepared by: Dr. Nasser Al-Qurainy 1 Objectives  By the end of this session the student should be able to:  Define virulence factors and pathogenicity of bacteria  Describe bacteria...

Pathogenicity of Bacteria Click to edit Master subtitle style Prepared by: Dr. Nasser Al-Qurainy 1 Objectives  By the end of this session the student should be able to:  Define virulence factors and pathogenicity of bacteria  Describe bacterial pathogenesis in terms of virulence factors that allow bacteria to enter, attach, and invade the human body, bacterial exotoxins, and endotoxins  Explain how bacteria ‘switch’ surface antigens to overcome the immune response 2 Overview Pathogenicity: The ability of a microorganism to cause disease Some microorganism are unequivocally pathogenic, while others are generally harmless Virulence: The degree of pathogenicity of a microorganism. This can be quantified by how many organisms are required to cause disease in fifty percent of those exposed to the pathogen ID50  I= Infectious, D= Dose ID50  Number of organisms required to cause disease in 50% of those exposed to the pathogen (e.g. dose of bacteria that causes disease in 50% test animals) LD50  L= Lethal, D=Dose LD50  Number of organisms required to kill 50% of those exposed to the pathogen (e.g. dose of bacteria that kills 50% test animals) 3 So how do bacteria cause infections? The answer is complex, but it involve host susceptibility to bacterial infections which influenced by a complex interplay of various factors.  Bacteria-related factors:  Ability to invade the host  Ability to persist within the host  Host-related factors:  Overall susceptibility  Immune response 4 Bacterial Pathogenesis Summary  Steps of bacterial pathogenesis: (1) Bacterial exposure to host through air, food, infected person, and environment. (2) Colonization of the bacteria inside host within specific organs, tissues, and cells, (3) Evasion of immune response through diverse strategies (4) Generating negative impact on host by causing infection. 5 Bacterial Pathogenesis Summary Elimination of the microbe without a disease, or Infectious disease, tissue damage and impairment of body function. 6  Virulence factors A bacterial product or strategy that contributes to virulence or pathogenicity. Different bacteria (and strains) produce different virulence factors Main categories: (i) Those that promote colonisation and invasion (invasiveness) (ii) Those that promote immune evasion (iii) Those that damage host (toxicity) 7  Virulence factors i. Colonisation and invasion 8 I. Colonisation and invasion 1. Entry into the host:  First step of infectious process is the entry of the microorganism into the host.  The entry is facilitated by one of several ports: the respiratory tract, gastrointestinal tract (GI), urogenital tract, or skin (cut, punctured, or burned) 9 I. Colonisation and invasion  Bacterial adherence is a key virulence factor to prevents bacteria from being removed by mucus or fluids.  Adherence also allows each attached bacterial cell to form a microcolony.  Mechanisms of Adherence: A. Pili and Fimbriae: Pili and fimbriae are hair-like appendages on the surface of bacteria Pili (singular: pilus): Longer, less numerous appendages that involved in attachment and genetic exchange. Fimbriae (singular: fimbria): Shorter, more numerous structures primarily involved in adhesion to host tissues and surfaces, facilitating colonization 10 I. Colonisation and invasion B. Surface Adhesion Molecules: Are specialized proteins or glycoproteins found on the bacterial cell surface that facilitate the attachment of the bacteria to host cells. These molecules bind specifically to receptors on the host cell membrane, allowing the bacteria to adhere tightly and resist removal by mechanical forces such as fluid flow. e.g., fibronectin-binding proteins in Staphylococcus aureus C. Hydrophobic Cell Walls: Some bacterial cell surfaces have a high affinity for water-repelling (hydrophobic) interactions, which allow the bacteria to adhere to host cell membranes and other surfaces. These interactions help bacteria resist being washed away by fluids like mucus or urine in the host. 11 Colonisation and invasion 2. Invasiveness:  Invasive bacteria have the ability to: Enter host cells Penetrate mucosal surfaces Spread from the initial site of infection  Invasiveness is facilitated by bacterial enzymes and spread beyond the initial infection site.  Collagenase: Degrades collagen, a major component of the extracellular matrix.  Hyaluronidase: Breaks down hyaluronic acid, which holds cells together in the extracellular matrix. 12 Virulence factors ii. immune evasion 13 II.Immune evasion 1. Polysaccharide capsules  Protective outer layers found in many bacteria. These capsules are primarily composed of polysaccharides (long chains of sugar molecules)  Bacteria with capsules (such as S. pneumoniae & N. meningitidis) have a better chance of surviving phagocytosis, acidic environments and other hydrolytic and proteolytic enzymes. 2. Protein A  Is a surface protein found in the cell wall of Staphylococcus aureus.  Protein A has a high affinity for the Fc region of immunoglobulin G (IgG) antibodies. This binding can help S. aureus evade the host immune system by preventing the opsonization and phagocytosis of the bacteria. 14 II.Immune evasion 3. Antigenic switching  Is the process by which pathogen alter the proteins or polysaccharides on their surface to evade the host immune system.  This variation helps bacteria survive and persist within the host by avoiding detection and destruction by the host's immune defenses. 15 Antigenic switching  Phase variation Genetically reversible ability of certain bacteria to turn off and turn on the expression of genes coding for surface antigens  Antigenic variation  Involves the modification of the gene for an expressed surface antigen by genetic recombination with one of many variable unexpressed DNA sequences. These changes are permanent in gene expression different antigenic structures of the surface antigen Antigenic variation in the gonococcus 16  Virulence factors iii. Host tissue damage (toxins) 17 III. Host tissue damage (toxins) A B Bacterial toxins: Some bacteria cause disease by producing toxic substances called toxins. 1. Exotoxins  Proteins secreted by both Gram-positive and Gram-negative bacteria  Can be some of the most poisonous substances known  1ug of Tetanus toxin can kill an adult human  Exotoxins generally have 2 components (AB subunit): B binds to the host cell and A is responsible for the toxic effect  Exotoxin effects  block protein synthesis / paralysis  Exotoxin examples: Diphtheria toxin, Tetanus toxin  Most exotoxins are rapidly inactivated by rapid heating (60° C) 18 III. Host tissue damage (toxins) 2. Endotoxins  These are not secreted but are integral components of the cell walls (LPS) of Gram- negative bacteria only  They are released into the host’s circulation after bacterial cell lysis  Effects: Fever, shock, hypotension, thrombosis  septic shock  Lipopolysaccharides (LPS) consists of:  O antigen (repeating sugar subunits)  Core polysaccharide (outer & inner)  Lipid component called Lipid A  Lipid A responsible for toxic effects of endotoxin 19 Exotoxins Vs Endotoxins 20 Thank you PAGE 21