Bacterial Pathogenesis and Virulence Factors

Bacterial Pathogenesis

• Bacterial pathogenesis is the process through which bacteria cause disease.
• The degree to which disease is caused is called virulence.
• Virulence factors are genetic traits that cause damage to the host.
• Bacteria cause disease by byproducts like gas and acids leading to direct tissue damage.
• Bacteria can also cause disease by releasing toxins into the bloodstream.
• These toxins travel to various organs causing harm.
• Virulence includes invasiveness and toxigenicity.

Bacterial Virulence Factors

• These are elements that are essential for invasion, dissemination, and pathogenicity.
• Examples include:
  • Virulent surface proteins
  • Iron-binding proteins
  • Exotoxins
  • Virulence plasmids
  • Toxin-producing phages
  • Capsules
  • Adhesins
  • Lipopolysaccharides (LPS)
  • Flagella

Introduction

• Bacteria have the ability to invade, adhere, and colonize environments.
• Bacteria can gain access to food in order to survive.
• Bacteria can evade the host's immune system.
• Bacteria create a niche or colony for themselves.
• Byproducts of growth (acids, gases) can lead to damage and harm to the host.

Mechanisms of Bacterial Pathogenicity

• Invasiveness: The ability to invade tissues.
  • Colonization - adherence and initial multiplication.
  • Production of substances to facilitate invasion.
  • Ability to evade or bypass host defence mechanisms.
• Toxigenesis: The ability to produce toxins.

Colonization, Adhesion, and Invasion

• Colonization is the establishment of the pathogen.
• The pathogen starts at an appropriate point of entry and establishes a colony.
• Colonization depends on environmental conditions.
• Some pathogens do not spread efficiently at higher temperatures.

Adherence

• Bacteria have adhesins that bind to specific receptors.
• These receptors keep the bacteria from being washed away.
• Glycocalyx and fimbriae(attachment pili) are involved in adherence.

Microbial Adhesions

• Most microbial adhesions are glycoproteins or lipoproteins located on the glycocalyx.
• They can also be found on capsules, capsids, pili, fimbriae or flagella.

Invasion

• Bacterial invasion is aided by the production of extracellular substances called invasins.
• Invasins are mostly proteins and enzymes that either destroy barriers or penetrate cells.
• Damage to the host by this process becomes the underlying pathology of a disease.

Pathogenic Actions of Bacteria

• Bacteria cause damage through 3 general mechanisms:
  • Direct damage or tissue destruction
  • Toxin-induced damage
  • Hypersensitivity reactions

Toxin-Induced Damage

• Toxins are bacterial products that directly harm tissues or initiate destructive biological processes.
• Toxins can cause cell lysis.
• Toxins can be categorised as exotoxins or endotoxins.

Toxins: Exotoxin and Endotoxin Classifications

• Exotoxins are produced by both Gram-positive and Gram-negative bacteria.
  • Proteins that are often released from cells.
  • Many different types based on structure and function.
  • Heat-liable and can be converted to toxoids.
  • Bind to specific receptors on host target cells.
• Endotoxins are produced only by Gram-negative bacteria.
  • Part of the cell wall (lipids A).
  • Only one type.
  • Heat-stable
  • Affects diverse range of host cells and systems.
  • Toxoids cannot be made.

Endotoxins

• Released when bacteria are killed by phagocytosis or antibiotics.
• NOT tissue or organ-specific, they cause general damage (fever, hypotension, weakness) to the host.

Endotoxin-Mediated Toxicity

• Symptoms include fever, leukopenia followed by leukocytosis, complement activation, thrombocytopenia, disseminated intravascular coagulation, reduced peripheral circulation, shock, and death.

Exotoxins

• 5 types, and each type is target-specific. Examples are:
• Enterotoxins
• Neurotoxins
• Cytotoxins
• Hematologic toxins
• Super antigens

Super Antigens

• Substances that hyper-stimulate lymphocytes and induce an immune response that is thousands of times stronger than normal.
• Result in a rapid increase in vasodilation and decrease in blood pressure, leading to shock.

Host Factors

• Host Factors play important roles in bacterial pathogenesis, including congenital defects and immunodeficiency
• Other diseases related to various conditions increase a person's susceptibility to infection.

Immunopathogenesis

• The host's immune response is the primary cause of disease symptoms in patients with bacterial infections.
• Symptoms are usually due to innate, immune, and inflammatory responses triggered by the infection.

Mechanisms for Escaping Host Defenses

• Bacteria attempt to avoid the immune system's clearance of them.
  • Examples include encapsulation, antigenic mimicry, masking using external components mimicking host cells.
• These methods make the microbe less visible to the host immune system and/or resist enzymes.

Summary: Bacterial Virulence Mechanisms

• Adherence (Colonization)
• Invasion
• Degradative enzymes
• Exotoxins
• Endotoxin
• Evasion of phagocytic & immune clearance
• By products of growth (gas, acid)
• Super antigens
• Escaping host defenses

References

• Medical Microbiology by Murray, Rosenthal Pfeiffer
• 7th Edition, Chapter 14
• Images from both Murray and Google.

Test your knowledge about the mechanisms of bacterial colonization, the roles of adhesins and invasins, and the differences between exotoxins and endotoxins. This quiz covers the pathogenic damage mechanisms and the genetic traits that enable bacteria to cause human disease, providing a comprehensive overview of bacterial virulence.