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Microbiology
Table of Contents
Unit 15 Overview: Microbial Mechanisms of Pathogenicity
15.1 Characteristics of Infectious Disease
15.2 How Pathogens Cause Disease
15.3 Virulence Factors of Bacterial and Viral Pathogens
15.4 Virulence Factors of Eukaryotic Pathogens

🦠microbiology review

15.3 Virulence Factors of Bacterial and Viral Pathogens

Citation:

Bacterial and viral pathogens have evolved clever ways to outsmart our bodies. They use sneaky tools called virulence factors to invade, hide, and wreak havoc. These factors help germs slip past our defenses and cause all sorts of nasty symptoms.

Bacteria pack a one-two punch with endotoxins and exotoxins. Viruses are masters of disguise, constantly changing to dodge our immune system. Understanding these tricks helps us develop better ways to fight back against infections.

Bacterial Virulence Factors

Virulence factors and disease symptoms

  • Virulence factors enhance pathogens' ability to cause disease by enabling invasion of host tissues, evasion of immune responses, and damage to host cells
  • Symptoms of infectious diseases result from direct effects of virulence factors (tissue damage, disruption of cellular functions, toxin production) and the host's immune response (inflammation, fever, systemic symptoms)

Endotoxins vs exotoxins

  • Endotoxins are lipopolysaccharides (LPS) integral to the outer membrane of gram-negative bacteria
    • Released during bacterial cell lysis or division
    • Heat-stable and resistant to denaturation
    • Stimulate strong innate immune response leading to inflammation and potential septic shock
  • Exotoxins are proteins secreted by both gram-positive and gram-negative bacteria
    • Secreted during bacterial growth and can act at distant sites from the infection
    • Heat-labile and can be denatured by heat or chemicals
    • Highly specific effects on host cells and tissues
    • Often delivered through bacterial secretion systems

Types of exotoxins

  • A-B toxins have two subunits: A (active) and B (binding)
    • B subunit binds to specific host cell receptors facilitating A subunit entry
    • A subunit has enzymatic activity that disrupts host cell functions
    • Cholera toxin, diphtheria toxin, and anthrax toxin are examples of A-B toxins
  • Membrane-disrupting toxins form pores in host cell membranes leading to cell lysis
    • Streptolysin O (Streptococcus pyogenes) and alpha-toxin (Clostridium perfringens) are examples
  • Superantigens stimulate massive, non-specific T cell activation causing a cytokine storm
    • Bind to MHC II molecules on antigen-presenting cells and T cell receptors bypassing normal antigen processing
    • Toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins are examples of superantigens

Regulation and delivery of virulence factors

  • Virulence gene regulation allows bacteria to adapt to different host environments
  • Bacterial secretion systems deliver virulence factors directly into host cells
  • Immune evasion strategies help pathogens avoid host defenses

Viral Virulence Factors

Viral strategies for host invasion

  • Viral adhesion to host cells occurs through interactions between viral surface proteins and specific host cell receptors
    • Influenza virus hemagglutinin binds to host cell sialic acid receptors
    • HIV gp120 binds to CD4 receptors on T cells and macrophages
  • Viruses evade host immune responses through various mechanisms:
    1. Antigenic drift: mutations in viral surface proteins lead to escape from neutralizing antibodies (influenza viruses, HIV)
    2. Antigenic shift: reassortment of viral genome segments results in novel surface proteins (influenza A viruses)
    3. Viral proteins interfere with host immune signaling pathways
      • Influenza NS1 protein inhibits interferon production
      • Herpes simplex virus ICP47 protein inhibits MHC I antigen presentation
    4. Integration into host genome (retroviruses) or establishment of latency (herpesviruses) allows viruses to persist undetected in the host

Key Terms to Review (48)

A-B exotoxins: A-B exotoxins are bacterial proteins consisting of two components: an 'A' (active) part that exerts toxic effects, and a 'B' (binding) part that facilitates entry into host cells. These toxins disrupt cellular processes, often leading to disease symptoms.
Adhesins: Adhesins are surface structures on pathogens that allow them to adhere to host cells. They play a crucial role in the initial stages of microbial infection.
Cholera toxin: Cholera toxin is a protein complex secreted by the bacterium Vibrio cholerae. It disrupts ion transport in the intestines, leading to severe diarrhea.
Efflux pumps: Efflux pumps are membrane proteins that actively export harmful substances out of microbial cells, contributing to antibiotic resistance. They play a crucial role in maintaining cellular homeostasis by removing toxic compounds.
Salmonella pathogenicity islands: Salmonella pathogenicity islands (SPIs) are distinct genetic regions in the Salmonella genome that encode various virulence factors. These regions are crucial for the bacteria's ability to cause disease and adapt to different environments.
Superantigens: Superantigens are a class of antigens that result in excessive activation of the immune system by non-specifically binding to T-cell receptors and major histocompatibility complex molecules. This leads to a massive release of cytokines, causing severe inflammatory responses.
Staphylococcal enterotoxins: Staphylococcal enterotoxins are exotoxins produced by Staphylococcus aureus that cause gastrointestinal illness. They function as superantigens, inducing an intense immune response.
Virulence factors: Virulence factors are molecules produced by pathogens that contribute to the pathogenicity and severity of infections. They help the microorganism invade the host, evade the immune system, and obtain nutrients.
Pathogenicity Islands: Pathogenicity islands are specialized regions of the bacterial genome that contain clusters of genes encoding virulence factors. These genetic elements play a crucial role in the ability of pathogenic bacteria to infect and cause disease in their hosts, connecting the concepts of how asexual prokaryotes achieve genetic diversity and the virulence factors that contribute to bacterial and viral pathogenesis.
Biofilm Formation: Biofilm formation is the process by which microorganisms, such as bacteria and fungi, adhere to surfaces and develop into complex, structured communities encased in a self-produced extracellular matrix. This phenomenon is closely linked to the pathogenesis and persistence of various microbial infections, as well as the effectiveness of antimicrobial agents and disinfectants.
Efflux Pumps: Efflux pumps are specialized transport systems found in the cell membranes of bacteria and other microorganisms that actively expel harmful substances, such as antibiotics and toxins, out of the cell. These pumps play a crucial role in the development of antimicrobial resistance and the virulence of bacterial pathogens.
Adhesins: Adhesins are specialized surface molecules found on the cells of many pathogens that enable them to attach to and infect host cells. They act as the 'sticky' components that facilitate the initial stages of pathogenesis by allowing the pathogen to bind to and invade the host's tissues.
Two-Component Systems: Two-component systems are signaling pathways commonly found in bacteria and other microorganisms that allow them to sense and respond to changes in their environment. These systems typically consist of a sensor histidine kinase and a response regulator that work together to initiate an appropriate cellular response.
Alpha-Toxin: Alpha-toxin is a potent exotoxin produced by the bacterium Staphylococcus aureus, a common pathogen that can cause a wide range of infections in humans. This virulence factor is known for its ability to disrupt cell membranes, leading to cell lysis and tissue damage, which is a key mechanism in the pathogenesis of various Staphylococcal infections.
Streptolysin O: Streptolysin O is a potent cytotoxin produced by various streptococcal bacteria, including Streptococcus pyogenes, that functions as a virulence factor by disrupting the cell membranes of host cells. It is a key component in the pathogenesis of certain streptococcal infections.
NS1 Protein: The NS1 protein is a non-structural protein expressed by various viruses, including influenza viruses, that plays a crucial role in viral pathogenesis and the evasion of the host's immune response. It is a key virulence factor that contributes to the ability of these viruses to cause severe disease in infected individuals.
Virulence Gene Regulation: Virulence gene regulation refers to the mechanisms by which pathogenic microorganisms control the expression of genes responsible for their ability to cause disease, or virulence. This term is closely tied to the understanding of how bacterial, viral, and eukaryotic pathogens modulate their virulence factors to successfully infect and harm their hosts.
Endotoxins: Endotoxins are complex lipopolysaccharide (LPS) molecules that are an integral part of the outer membrane of Gram-negative bacteria. They are released upon the lysis or death of the bacterial cell and can trigger a severe inflammatory response in the host, contributing to the virulence of these pathogens.
Neuraminidase: Neuraminidase is an enzyme found on the surface of influenza viruses that plays a crucial role in the virulence and pathogenicity of these viral pathogens. It is a key virulence factor that enables the influenza virus to infect and spread effectively within the host.
Host Cell Receptors: Host cell receptors are specialized molecules found on the surface of host cells that act as docking sites for pathogens, allowing them to attach and gain entry into the cell. These receptors play a crucial role in the initial stages of infection by facilitating the recognition and binding of viruses, bacteria, and other microorganisms to their target host cells.
ICP47 Protein: ICP47 is a protein encoded by the herpes simplex virus (HSV) that functions as a virulence factor by interfering with the host's immune response. It is a key component in the viral evasion of the host's cytotoxic T-cell response, a crucial part of the adaptive immune system.
Actin Cytoskeleton: The actin cytoskeleton is a dynamic network of filamentous actin proteins that provide structural support and facilitate various cellular processes within eukaryotic cells. It plays a crucial role in the context of virulence factors of bacterial and viral pathogens.
Tight Junctions: Tight junctions are specialized cell-to-cell adhesion complexes that form continuous seals between adjacent epithelial cells. They act as physical barriers, regulating the movement of molecules and ions through the paracellular space, and are crucial in maintaining the integrity of epithelial tissue layers, such as those found in the skin, gastrointestinal tract, and blood-brain barrier.
Anthrax Toxin: Anthrax toxin is a potent virulence factor produced by the bacterium Bacillus anthracis, the causative agent of the deadly disease anthrax. This complex toxin plays a crucial role in the pathogenesis of anthrax and is a key target for understanding bacterial virulence and the development of countermeasures.
Superantigens: Superantigens are a unique class of antigens that are capable of activating a large fraction of T cells, leading to a massive release of inflammatory cytokines and potentially life-threatening conditions. They are closely associated with the virulence of certain bacterial and viral pathogens, as well as the modulation of the host's cellular immune response.
Toxic Shock Syndrome Toxin-1: Toxic Shock Syndrome Toxin-1 (TSST-1) is a potent exotoxin produced by certain strains of Staphylococcus aureus bacteria. It is a key virulence factor that contributes to the development of the life-threatening condition known as toxic shock syndrome.
A-B Toxins: A-B toxins are a class of bacterial exotoxins that consist of two distinct subunits: an enzymatically active A subunit and a cell-binding B subunit. These toxins are potent virulence factors produced by certain pathogenic bacteria, allowing them to hijack host cellular processes and cause severe disease in humans and animals.
Cytokine Storm: A cytokine storm is an excessive and uncontrolled release of pro-inflammatory cytokines in response to an infection or other trigger. This dysregulated immune response can lead to severe inflammation, tissue damage, and potentially life-threatening complications, making it a key virulence factor for both bacterial and viral pathogens.
Immune Evasion: Immune evasion refers to the strategies employed by pathogens to circumvent, subvert, or suppress the host's immune defenses, allowing them to establish and maintain infection. This term is crucial in understanding how pathogens cause disease, the virulence factors they possess, and the mechanisms behind viral infections in various body systems.
Bacterial Secretion Systems: Bacterial secretion systems are specialized mechanisms employed by pathogenic bacteria to transport and secrete various proteins and toxins outside the bacterial cell. These secretion systems play a crucial role in the virulence and pathogenicity of bacterial infections.
Exotoxins: Exotoxins are potent, soluble, and heat-labile proteins secreted by certain pathogenic bacteria that can cause severe damage to host cells and tissues. These toxins are released outside the bacterial cells and can travel through the bloodstream to target specific organs or systems, contributing to the virulence and pathogenicity of the bacteria.
Invasins: Invasins are bacterial virulence factors that facilitate the invasion and penetration of host cells by pathogens. They are crucial for the pathogenesis of many bacterial and viral infections, as well as certain eukaryotic pathogens, by enabling them to breach host barriers and establish an intracellular niche.
Staphylococcal Enterotoxins: Staphylococcal enterotoxins are a group of potent exotoxins produced by Staphylococcus aureus, a common bacterial pathogen. These toxins are responsible for the symptoms associated with staphylococcal food poisoning and can also modulate the host's immune response, making them relevant in the context of bacterial virulence factors, T lymphocyte function, and bacterial infections of the circulatory and lymphatic systems.
Virulence Factors: Virulence factors are specific characteristics or mechanisms that enable pathogens, such as bacteria, viruses, and eukaryotic organisms, to cause disease and harm the host. These factors contribute to the pathogenicity and severity of an infection by enhancing the pathogen's ability to invade, colonize, and evade the host's immune defenses.
Toxins: Toxins are poisonous substances produced by living organisms, such as bacteria, plants, and animals, that can cause harm or death to other organisms, including humans. These substances are integral to the virulence and pathogenicity of many pathogens, allowing them to infect, damage, and disrupt normal bodily functions.
Cholera Toxin: Cholera toxin is a potent exotoxin produced by the bacterium Vibrio cholerae, the causative agent of the severe diarrheal disease cholera. This toxin is a key virulence factor that contributes to the pathogenesis of cholera, a major bacterial infection of the gastrointestinal tract.
Diphtheria Toxin: Diphtheria toxin is a potent exotoxin produced by the bacterium Corynebacterium diphtheriae, the causative agent of the serious infectious disease diphtheria. This toxin is a key virulence factor that contributes to the severity and pathogenesis of diphtheria infections.
Type III Secretion System: The type III secretion system (T3SS) is a specialized molecular machinery found in many Gram-negative bacterial pathogens. It serves as a key virulence factor, allowing these bacteria to directly inject effector proteins into the host cell, modulating its cellular processes and facilitating infection.
Pathogenicity: Pathogenicity refers to the ability of a microorganism, such as a bacterium, virus, or fungus, to cause disease in a host. It encompasses the various mechanisms and factors that contribute to a pathogen's capacity to infect, proliferate, and induce harmful effects within the host's body.
Quorum Sensing: Quorum sensing is a communication mechanism used by bacteria to coordinate gene expression and behavior in response to changes in cell population density. It allows bacteria to sense and respond to the presence of other bacteria, enabling them to act in a coordinated manner as a community rather than as individual cells.
Lipopolysaccharides: Lipopolysaccharides (LPS) are complex molecules found in the outer membrane of gram-negative bacteria, playing a crucial role in their structure, function, and interaction with the host immune system. These unique lipid-carbohydrate compounds are central to understanding the biology and pathogenicity of various bacterial species.
Antigenic Drift: Antigenic drift is a gradual, continuous process of genetic changes that occur in the surface proteins of viruses, particularly influenza viruses, leading to the emergence of new viral strains. This evolutionary mechanism allows the virus to evade the host's immune system and cause recurring infections.
Gp120: gp120 is a glycoprotein found on the surface of the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). It plays a crucial role in the virus's ability to infect and enter human cells, making it a key virulence factor in the pathogenesis of HIV/AIDS.
Hemagglutinin: Hemagglutinin is a glycoprotein found on the surface of certain viruses, such as influenza viruses, that allows the virus to bind to and agglutinate (clump together) red blood cells. This crucial step in the viral life cycle facilitates the virus's ability to infect host cells and spread throughout the body.
Antigenic Shift: Antigenic shift is a major, abrupt, and unexpected change in the surface antigens of a virus, particularly in influenza viruses. This phenomenon results in the emergence of a new viral strain that is significantly different from previous strains, often leading to the potential for widespread outbreaks and pandemics.
Lipases: Lipases are enzymes that catalyze the hydrolysis of lipids, breaking down complex fat molecules into simpler components like fatty acids and glycerol. These enzymes play crucial roles in the catabolism of lipids, as well as serving as important virulence factors for certain pathogens.
Proteases: Proteases are enzymes that catalyze the breakdown of proteins into smaller peptides or amino acids. They play crucial roles in various biological processes, including the catabolism of lipids and proteins, the virulence of bacterial, viral, and eukaryotic pathogens, and the regulation of fungal infections in the reproductive system.
Beta-Lactamases: Beta-lactamases are enzymes produced by bacteria that confer resistance to beta-lactam antibiotics, such as penicillins and cephalosporins, by hydrolyzing the beta-lactam ring and rendering the antibiotics ineffective. These enzymes play a crucial role in the ability of bacteria to achieve genetic diversity, develop drug resistance, and exhibit virulence factors.