Pathogenesis of Bacterial Infection

Pathogenesis of Bacterial Infection

• Pathogenesis refers to how microorganisms cause disease.
• Pathogens are microorganisms capable of causing disease.
• Pathogenicity is the ability to cause disease, while virulence refers to the severity or capacity of a microorganism to cause disease.

Normal Flora vs. Virulent & Opportunistic Pathogens

• Less than 1% of bacteria can cause disease in humans.
• The majority of bacteria in the human body are part of the normal flora or microbiome, which are typically non-pathogenic.
• Normal flora can cause infection if they escape their usual location, a barrier is breached, or the host is immunosuppressed.
• Virulent bacteria have an increased ability to invade or damage the host.
• Primary pathogens can cause disease as a result of their presence in the host, even if they are among normal flora without causing disease.
• Virulence factors are genetic, biochemical, or structural features of a pathogen that enhance its ability to produce disease.
• Opportunistic bacteria have low intrinsic virulence and typically don't cause infections in healthy patients.
• Opportunistic infections can occur in immunocompromised individuals or when a foreign body is present.

Transmission and Infection

• Bacteria must first enter the body through a portal of entry, including ingestion, inhalation, penetration, sexual transmission, or vertical transmission.
• Adhesins are bacterial protein ligands enabling adherence to host cells, preventing clearance from the host.
• Invasins are bacterial proteins that damage host cells and facilitate spread and invasion.

Immune Evasion

• Bacteria have developed mechanisms to avoid immune clearance, including:
  • Inhibition of phagocytosis: Capsular polysaccharides can prevent phagocytosis.
  • Survival within phagocytes: Bacteria can escape the phagosome, prevent phagosome-lysosome fusion, or survive within the phagolysosome.
  • Immune cell destruction: Some bacteria produce enzymes like leucocidins, streptolysin, and coagulase to target immune cells or prevent their function.

Damage to Host Cells

• Bacterial enzymes, including invasins, toxins, and superantigens, damage host cells.

Toxins: Exotoxins vs. Endotoxins

• Exotoxins are proteins produced by living bacteria, primarily Gram-positive bacteria, and secreted or released during cell lysis. They can act locally or distally.
• Endotoxins are integral parts of the bacterial cell envelope, primarily from Gram-negative bacteria, released during cell lysis or turnover.
• Superantigens are a type of exotoxin that hyperactivate the immune system, causing a shock syndrome.
• Exotoxins are generally more potent than endotoxins.

Dissemination of Pathogens

• Pathogens can spread in the body through:
  • Tissue or tissue plane spread
  • Haematogenous spread (through the bloodstream)
  • Lymphatic spread (through the lymphatic system)
  • Carriage within macrophages
  • Ascending or descending spread within a tract

Transmission of Pathogens

• Transmission of pathogens can occur through:
  • Person-to-person direct contact
  • Respiratory transmission (coughing, sneezing)
  • Gastrointestinal transmission (diarrhea)
  • Sexual transmission (genital discharge or ulcers)
  • Vertical or perinatal transmission (from mother to child during pregnancy, delivery, or shortly after birth)

Host Risk Factors

• Host factors that increase susceptibility to infection and potentially worsen infection severity include:
  • Extremes of age
  • Diabetes
  • Immunosuppression (disease-induced or medication-induced)
  • Major breach in skin or mucosa (e.g., recent major surgery)
  • Prosthetic material (e.g., IV lines, catheters, ventilators)
  • Anatomical abnormalities or malfunctions
  • Antibiotic therapy (e.g., Clostridium difficile infection)

Pathogenesis of Bacterial Infection

• Pathogenesis is the mechanism by which a microorganism causes disease.
• Pathogen: A microorganism capable of causing disease.
• Pathogenicity: The ability of an organism to cause disease.
• Virulence: The degree or severity of a pathogen's ability to cause disease.

Differentiate Normal Flora From Pathogens

• Normal flora (microbiome): Microorganisms residing in or on the body without causing disease, commonly non-pathogenic.
• Virulent bacteria: Organisms which have an increased ability to invade or damage the host, can be primary pathogens capable of causing disease due to their presence.
• Opportunistic bacteria: Microorganisms with low intrinsic virulence, can cause serious infection in immunocompromised individuals or in the presence of foreign bodies.

Transmission and Entry Of Pathogens

• Portals of entry:
  • Ingestion (e.g., Salmonella food poisoning)
  • Inhalation (e.g., Tuberculosis)
  • Penetration (e.g., HIV)
  • Sexual (e.g., Chlamydia)
  • Vertical (e.g., Group B Streptococcus)
• Adhesion: Bacterial attachment to host cells is crucial for establishing a stable population and preventing clearance by the immune system. Adhesins, small bacterial protein ligands, recognize specific receptors on host cells.
• Invasion: This process involves pathogens employing biochemical virulence factors called “Invasins” which can damage host cells and facilitate spread.

Immune Evasion

• Immune evasion: Pathogens have developed mechanisms to avoid being killed by the immune system:
  • Inhibition of phagocytosis: Capsules composed of polysaccharides can prevent phagocytosis by immune cells.
  • Survival within phagocytes: Some pathogens can escape the phagosome, prevent phagosome/lysozyme fusion, or survive within the phagolysosome.
  • Immune cell destruction/evasion: Bacteria may produce enzymes that directly target immune cells or prevent their function, such as leucocidins, streptolysin, and coagulase.

Damage To Host Cells

• Bacterial enzymes: These can damage host cells and are important for immune evasion. Examples include invasins, toxins, and superantigens.

Endotoxins and Exotoxins

• Exotoxins: Polypeptide molecules produced by living bacteria, usually secreted or released during cell lysis. They can act locally or distally and target specific cells.
• Endotoxins: Integral parts of the bacterial cell envelope, released due to cell lysis or turnover. LPS (Lipopolysaccharide) is a prototypical example, found in Gram-negative bacteria. Endotoxins can induce a pro-inflammatory cascade leading to septic shock.

Dissemination of Pathogens in The Body

• Spread:
  • Through tissues or tissue planes
  • Haematogenous (bloodstream)
  • Lymphatic (lymph system)
  • Carriage within macrophages
  • Ascending/descending through a tract
• Transmission:
  • Person-to-person by direct contact
  • Respiratory (coughing, sneezing)
  • Gastrointestinal (diarrhea)
  • Sexually (genital discharge/ulcer)
  • Vertical & perinatally

Host Risk Factors

• Factors increasing susceptibility to infection:
  • Extremes of age
  • Diabetes
  • Immunosuppression (disease-induced or medication-related)
  • Major breach in skin/mucosa
  • Prosthetic materials
  • Anatomical abnormality or malfunction
  • Antibiotic therapy

Pathogenesis of Bacterial Infection

• Pathogenesis refers to the mechanisms by which microorganisms cause disease.
• Pathogen is a microorganism that can cause disease.
• Pathogenicity refers to the ability of a microorganism to cause disease.
• Virulence refers to the severity of the disease caused by a pathogen.

Normal Flora (Microbiome)

• The normal flora, also known as the microbiome or microbiota, are microorganisms that reside in or on our bodies without causing disease.
• These microorganisms are mostly non-pathogenic, meaning they do not cause disease.
• However, they can cause infection if they escape their usual location, a barrier is breached, or the host is immunosuppressed.

Virulent Bacteria

• Virulent bacteria possess an increased ability to invade or damage the host.
• Primary pathogens are able to cause disease as a result of their presence within the host.
• They may live among normal flora without causing disease in the host, in which case they are considered "colonized".
• Virulence factors are genetic, biochemical, or structural features of a pathogen that enable or enhance its ability to produce disease.

Opportunistic Bacteria

• Opportunistic bacteria have low intrinsic virulence and usually do not cause infections in non-immunocompromised patients.
• They may cause serious infections in certain circumstances, such as in immunocompromised individuals or in the presence of foreign bodies.

Infection

• The occurrence of an infection depends on the state of the host, the virulence of the organism, the size of the inoculum, and the portal of entry.

Transmission of Pathogens

• Pathogens can be transmitted through various portals of entry:
  • Ingestion: Examples include Salmonella food poisoning.
  • Inhalation: Examples include Tuberculosis.
  • Penetration: Examples include HIV.
  • Sexual: Examples include Chlamydia.
  • Vertical: Examples include Group B Streptococcus.

Bacterial Entry and Immune Evasion

• Bacteria utilize various mechanisms to gain entry into the body and evade the immune system:
  • Adhesion: Adhesins, small bacterial protein ligands, help establish a stable population of bacteria within the host by recognizing specific receptors on host cells.
  • Invasion: Invasins, proteins that can damage host cells and facilitate spread and invasion, help bacteria invade the host.
  • Immune Evasion: Bacteria can evade the immune system by:
    • Inhibition of phagocytosis: Capsule composed of polysaccharides prevents phagocytosis by immune cells.
    • Survival within phagocytes: Some bacteria can escape the phagosome, prevent phagosome/lysozyme fusion, or survive within the phagolysosome.
    • Immune cell destruction: Some bacteria can produce enzymes that directly target immune cells or prevent their function, such as leucocidins, streptolysin, and coagulase.

Host Cell Damage

• Bacteria can damage host cells through the production of enzymes and toxins:
  • Invasins: Damage host cells and facilitate spread and invasion.
  • Toxins: These are compounds that are toxic to host cells. There are two main types:
    • Endotoxins: These are integral parts of the bacterial cell envelope that are released upon cell lysis or turnover. Examples include lipopolysaccharide (LPS) found in Gram-negative bacteria.
    • Exotoxins: These are polypeptide molecules secreted by bacteria that can act locally or distally. They can be categorized as cytotoxins, neurotoxins, and enterotoxins.
  • Superantigens: These are a type of exotoxin that can hyperactivate the immune system leading to a shock syndrome.

Spread of Pathogens within the Body

• Pathogens can spread in the body via:
  • Spread through tissues or tissue planes
  • Haematogenous: Spread via the bloodstream.
  • Lymphatic: Spread via the lymphatic system.
  • Carriage within macrophages: Some bacteria can spread by “hiding” within macrophages.
  • Ascending/descending spread within a tract: Spread can occur within a specific tract, like the digestive system.

Host Risk Factors

• Certain factors can increase the susceptibility of a host to infection and increase the chances of severe infection:
  • Extremes of age: Infants and elderly individuals are more susceptible to infections.
  • Diabetes: Diabetes can impair immune function.
  • Immunosuppression: Various medical conditions or medications can suppress the immune system and increase susceptibility to infections.
  • Major breach in skin/mucosa: Surgical procedures or injuries can create an entry point for pathogens.
  • Prosthetic materials: Prosthetic devices can provide a surface for bacteria to colonize.
  • Anatomical abnormality or malfunction: Structural abnormalities or malfunctions can increase susceptibility to infections.
  • Antibiotic therapy: Antibiotics can disrupt the normal flora, allowing opportunistic bacteria to thrive.

This quiz covers the key concepts of bacterial pathogenesis, including definitions of pathogens, pathogenicity, virulence, and the differences between normal flora and pathogenic bacteria. Understand the mechanisms by which bacteria can cause disease and the factors that enhance their infectivity. Test your knowledge on how normal flora can become opportunistic pathogens under certain conditions.