Microbial Mechanisms of Pathogenicity PDF

# Chapter 15: Microbial Mechanisms of Pathogenicity ## Microbial Mechanisms of Pathogenicity: - **Pathogen:** Any microorganism that has the capacity to cause disease. - Pathogenic microorganisms have special properties that allow them to invade the human body or produce toxins. - **Pathogenic...

# Chapter 15: Microbial Mechanisms of Pathogenicity ## Microbial Mechanisms of Pathogenicity: - **Pathogen:** Any microorganism that has the capacity to cause disease. - Pathogenic microorganisms have special properties that allow them to invade the human body or produce toxins. - **Pathogenicity:** The ability of a pathogen to produce a disease by overcoming the defenses of the host: - Portals of entry - Penetrate host defenses - Damage host cells - Portal of exit - **Virulence:** The degree of pathogenicity that gives a quantitative measure of the pathogenicity or likelihood of causing disease. ## Microbial Mechanism of Pathogenicity: The pathogenicity of microbes occurs in following stages: - **Portals of Entry:** Microbes can enter the body through various portals like skin, mucous membranes - respiratory, gastrointestinal or genitourinary tract or the conjunctiva, and the parenteral route. - **Adherence:** Microbes attach to host cells by binding of their ligands/adhesins to host cell receptors via complementary chemical interactions. - **Penetration or Evasion of Host Defenses:** Once adhered, microbes evade host defenses like phagocytosis by using capsules, specific components of cell wall, releasing enzymes, undergoing antigenic variation or invading host cells. - **Damage to Host Cells:** Microbes damage host cells by using host nutrients (siderophores), direct damage by their metabolism, or by releasing toxins, which can be further categorized into exotoxins or endotoxins. - **Portals of Exit:** The same portals of entry are generally used as portals of exit for microbes, but they can also use arthropods, or syringes. ## Numbers of Invading Microbes: - **Virulence:** Can be expressed as: - **ID50:** Number of microbes that will cause a demonstrable infection in 50% of inoculated animals. This is also known as the Infectious dose. - **LD50:** Number of microbes that will kill 50% of inoculated test animals. This is also known as the Lethal Dose. ## Pathogenicity - Adherence: - **Colonization:** The first stage of microbial infection is the establishment of the pathogen at the appropriate portal of entry - **Adherence** is often an essential step in bacterial pathogenesis or infection because it is required for colonizing a new host: - **Adhesion:** Microorganisms attach themselves to cells by using **receptors** and **ligands**. - Bacterial adhesins can be chemical components of capsules, cell walls, glycocalyx, pili or fimbriae. - For viruses, it can be viral capsids, or components of the envelope. - Host receptors are usually glycoproteins located on the cell membrane or tissue surface - Interaction of ligand with host receptor can determine specificity for host cells. - Inability to make attachment proteins or adhesins renders the microorganisms avirulent - Ability to change or block the ligand or its receptor can prevent infection ## Biofilms: - Biofilms are masses of microbes and their extracellular products that facilitate the attachment of free-floating microorganisms to a surface using cell adhesion structures. - The first colonists facilitate the arrival of other cells and they can communicate via quorum sensing. - Biofilm grows through a combination of cell division and recruitment. - Microbes form a biofilm in response to many factors like cellular recognition of specific or non-specific attachment sites on a surface, nutritional cues and exposure of planktonic cells to sub-inhibitory concentrations of antibiotics. - Biofilms have been found to be involved in a wide variety of microbial infections in the body. - Biofilms play a role in making the infection antibiotic-resistant. ## How Bacterial Pathogens Penetrate Host Defenses: - **Capsules:** Some pathogens have capsules that prevent them from engulfment by phagocytes: - Streptococcus pneumoniae - Haemophilus influenzae - Bacillus anthracis - **Cell Wall Components:** Proteins in the cell wall can facilitate adherence or prevent a pathogen from being phagocytized. - **M protein:** resists phagocytosis in Streptococcus pyogenes - **Opa protein:** inhibits T helper cells in Neisseria gonorrhoeae - **Mycolic acid:** (waxy lipid) resists digestion in Mycobacterium tuberculosis ## How Bacterial Pathogens Damage Host Cells: - **Using the Hosts's Nutrients:** Siderophores are small, high-affinity iron chelating compounds secreted by microorganisms such as bacteria and fungi. - **Direct Damage:** Host cells can be destroyed when pathogens metabolize and multiply inside the host cells. - Disrupt host cell function - Produce waste products - **Toxins:** Most bacterial damage is carried out by toxins. ## Toxin Production: - **Toxins:** Poisonous substances produced by microorganisms. - **Toxigenicity:** The ability to produce toxins. - **Toxemia:** refers to the presence of toxins in the blood. - **Exotoxins:** Are produced by bacteria and released into the surrounding medium. They are proteins : Enzymes that carry out specific reactions. - **A-B toxins:** These are two-component protein complexes - **B:** Binds to host membrane - **A:** Active - They are soluble in body fluids, rapidly transported throughout the body in blood or lymph. - *Exotoxins, not the bacteria, produce the disease symptoms.* - Produced mainly by gram-positive bacteria. - **Endotoxins:** Are part of the outer portion of the cell wall (lipid A) of gram-negative bacteria. They are liberated when the bacteria die and the cell wall breaks apart. ## Exotoxins: - **Cytotoxins:** Kill or damage host cells. - Membrane-disrupting toxins lyse host's cells by: - Making protein channels in the plasma membrane - Disrupting phospholipid bilayer - **Neurotoxins:** Interfere with nerve impulses. - **Enterotoxins:** Affect lining of gastrointestinal tract. - **Antitoxins:** Provide immunity to toxins. - **Superantigen:** This toxin overstimulates the body's immune response due to release of cytokines from host cells. This can result in symptoms like fever, nausea, vomiting, diarrhea, shock, and death. - **Toxoids:** Toxins that have been altered by heat or chemicals. They are used as vaccines for diphtheria and tetanus. - Most genes for toxins are carried on plasmids or phages. ## Exotoxin vs Endotoxin: | Feature | Exotoxin | Endotoxin | |---|---|---| | Source | Mostly Gram-positive bacteria | Gram-negative bacteria | | Relation to microbe | By-products of growing cell | Part of outer membrane | | Chemistry | Protein | Lipid A | | Fever? | No | Yes | | Neutralized by antitoxin? | Yes | No | | LD50 | Small | Relatively large | ## Endotoxins: - Endotoxin is lipid portion of lipopolysaccharides (LPS), called lipid A. - It is part of outer membrane surrounding gram-negative bacteria. - Endotoxins are released by the bacteria when it dies due to: - Autolysis - External lysis mediated by complement and lysozyme - Phagocytic digestion of bacterial cells - Antibiotics - Endotoxins cause: - Fever (by inducing the release of interleukin-1) - Shock (because of a TNF-induced decrease in blood pressure) - Blood clotting - Tissue death - Death - Endotoxins can cause a weakening of the blood-brain barrier and allow more bacteria from the bloodstream to cross it. - Endotoxins do not promote the formation of effective antibodies. ## Endotoxins and The Pyrogenic Response: - Fever is a pyrogenic response caused by endotoxins. ## Plasmids, Lysogeny and Pathogenicity: - **Plasmids** may carry and spread through conjugation genes for: - **Antibiotic resistance** - **Toxins production** - **Capsules** - **Fimbriae** - **Lysogenic conversion** can result in bacteria after bacteriophage infection. - **Toxins production** - **Capsules** ## Exotoxins and Lysogenic Conversion: | Species | Exotoxin | Lysogeny | |---|---|---| | Corynebacterium diphtheriae | A-B toxin | + | | Streptococcus pyogenes | Membrane-disrupting erythrogenic toxin | + | | Clostridium botulinum | A-B toxin; neurotoxin | + | | C. tetani | A-B toxin; neurotoxin | + | | Vibrio cholerae | A-B toxin; enterotoxin | + | | Staphylococcus aureus | Superantigen | + | ## Pathogenic Properties of Viruses: - Viruses gain access to host cells because they have attachment sites for receptors on the host cell. - Viruses avoid the host’s immune response by growing inside cells. - Viruses cause: - **Cytocidal effects:** (cell death) - **Noncytocidal effects:** (damage but not death). - Visible signs of viral infections are called cytopathic effects (CPE). - Cytopathic effects include: - Stopping of mitosis - Lysis: Release of lysosomal enzymes - Transformation: Abnormal cells that have lost contact inhibition. - The formation of inclusion bodies - Cell fusion - Antigenic changes - On cell surface, causing destruction of infected cells by the immune system. - Chromosomal changes ## Pathogenic Properties of Fungi, Protozoa and Algae: - **Fungal infections** don't have well defined virulent factors. They can: - Secrete enzymes - Produce toxins - Cause allergic responses. - **Protozoa** can: - Cause damage to host tissue - Produce disease symptoms by releasing metabolic waste products - Change their surface antigens to avoid destruction by the host's antibodies. - **Some algae** produce neurotoxins that cause paralysis when ingested by humans. ## Portals of Exit: - **Just as pathogens have preferred portals of entry, they also have definite portals of exit.** - Where microbes leave the body - How they spread through the population - **Three common portals of exit are:** - The respiratory tract via coughing or sneezing - The gastrointestinal tract via saliva or feces - The genitourinary tract via secretions from the vagina or penis - **Arthropods and syringes** provide a portal of exit for microbes in blood. ## Learning Objectives: - Identify the principal portals of entry. - Define LD50 and ID50. - Using examples, explain how microbes adhere to host cells. - Explain how capsules and cell wall components contribute to pathogenicity. - Compare the effects of coagulases, kinases, hyaluronidase, and collagenase. - Define and give an example of antigenic variation. - Describe how bacteria use the host cell's cytoplasm to enter the cell. - Describe the function of siderophores. - Provide an example of direct damage, and compare this to toxin production. - Contrast the nature and effects of exotoxins and endotoxins. - Outline the mechanisms of action of A-B toxins, membrane-disrupting toxins, and superantigens. - Classify diphtheria toxin, erythrogenic toxin, botulinum toxin, tetanus toxin, Vibrio enterotoxin, and staphylococcal enterotoxin. - Using examples, describe the role of plasmids and lysogeny in pathogenicity. - List cytopathic effects of viral infections.