Mechanisms of Pathogenicity Flashcards
(32 cards)
Primary (True) Pathogens
- Cause disease in anyone, including otherwise healthy individuals
- Responsible for primary infections
Opportunistic pathogens
- Do not cause disease in otherwise healthy people
- Cause disease only in immunocompromised hosts
HAI (healthcare-associated infection)
- Acquired in any healthcare environment, including outpatient settings
- Includes primary care visits, pharmacies, clinics
Nosocomial infection
- Acquired during a hospital stay
- Requires admission (e.g., overnight stay)
- Often resistant to multiple drugs
Signs vs symptoms
- Signs: Objective, measurable indicators observed by others (e.g., fever, heart rate)
- Symptoms: Subjective experiences felt by the patient, not measurable by others (e.g., pain, fatigue)
- Key difference: Signs are externally observable; symptoms are internally experienced
Periods of Disease
-
Incubation – No signs or symptoms; pathogen present but person is asymptomatic
→ Low pathogen levels, may still transmit disease -
Prodromal – Vague, general signs and symptoms; person feels “off” but unclear cause
→ Pathogen levels increasing -
Illness – Signs and symptoms are most severe and characteristic of the disease
→ Pathogen levels peak -
Decline – Signs and symptoms begin to lessen in severity
→ Pathogen numbers decrease -
Convalescence – No signs or symptoms; recovery phase
→ Low pathogen levels may persist; person may still shed pathogen
Intoxication
- Disease caused by exposure to a microbial toxin, not the pathogen itself
- Organism may be absent or dead at time of exposure
- Illness results from toxin activity, not infection
- Example context: Botulinum toxin causes disease even after bacteria are killed
Stages of Pathogenesis
-
Exposure
- Pathogen encounters the host at a specific portal of entry
- Common routes: skin, respiratory tract, digestive tract, urogenital tract, parenteral route
- If the pathogen cannot access the correct portal, no infection occurs
-
Adhesion
- Pathogen attaches to host cells using surface molecules (e.g., adhesins)
- Must adhere in order to establish residence and initiate infection
-
Invasion
- Pathogen enters and spreads through host tissues
- Mechanisms: exoenzymes, exotoxins, membrane fusion, endocytosis
- Often includes evasion of host defenses, allowing the pathogen to persist
-
Infection
- Pathogen grows and multiplies in the host
- May remain localized, spread to adjacent areas (focal), or disseminate systemically
-
Transmission
- Pathogen exits the host through a portal of exit, enabling spread to new hosts
- Portals often mirror the entry route: skin, respiratory, digestive, urogenital, parenteral
Virulence
- Degree to which an organism is likely to cause disease after exposure
- Not a measure of disease severity
- Described by ID₅₀ (infectious dose that causes disease in 50% of hosts)
- Levels:
- Highly virulent – easily causes disease
- Virulent – can cause disease
- Avirulent – does not cause disease
Infectious dose
- Measures virulence: how many organisms are needed to cause disease in 50% of hosts
- Lower ID₅₀ = higher virulence
Viruses
- Norovirus: 1–10 particles → very virulent
- Rotavirus: 10–100 particles → less virulent, can be fatal in infants
Bacteria
- E. coli O157:H7: 10–100 → highly virulent, dangerous in children
- Shigella dysenteriae: 10–200 → very virulent
- Vibrio cholerae: ~1,000,000 → low virulence, but deadly if untreated (24 hrs)
Protozoa
- Giardia duodenalis: ID = 1 → very mild disease*
- Cryptosporidium parvum: 10–100 → can be severe, especially in immunocompromised
Note: Bacteria use chemical communication (quorum sensing), so ID range reflects threshold population size
Virulence Factors
Mechanisms or features that enable an organism to cause disease. Act at different stages of pathogenesis
Key Types
1. Attachment: adherence to host cells/tissues
2. Invasion: entry into host cells or tissues
3. Evasion: escape from immune defenses
4. Infection: features that promote or maintain infectious disease
An organism is pathogenic if it has features that allow it to behave like a pathogen
Virulence Factor: Attachment
Mechanisms that allow pathogens to adhere to host cells or tissues at the start of infection.
Key Types
1. Bacteria:
- Fimbriae: attach to host surfaces (e.g., microvilli)
- Glycocalyces: sticky outer coating increases adhesion
2. Viruses:
- Capsids and glycoprotein spikes bind specific host receptors
3. Eukaryotes:
- Adhesion discs, suckers, hooks, and barbs
Attachment is often the*first step in pathogenesis.
Virulence Factor: Invasion
Mechanisms that allow pathogens to enter host cells or tissues and spread within the body.
Key Types
1. Bacteria:
- Exoenzymes: degrade barriers to entry
- Exotoxins: damage host tissues
- Endocytosis: induced uptake by host cells
2. Viruses:
- Endocytosis or membrane fusion for cellular entry
Invasion enables pathogens to move beyond surface colonization and establish infection.
Virulence Factor: Evasion
Mechanisms that allow pathogens to avoid detection or destruction by the host immune system.
Key Types
1. Capsules: hide surface antigens, prevent phagocytosis (e.g., Streptococcus pneumoniae)
2. Exoenzymes & Exotoxins: damage or kill immune cells (e.g., leukocidins)
3. Antigenic variation: pathogens alter surface proteins to evade immune memory
- Antigenic drift: gradual changes (e.g., influenza virus)
- Borrelia: the spirochete that causes Lyme disease alters its OspC surface antigen over time
→ avoids recognition by host antibodies
→ changes result from gene regulation shifts that keep it one step ahead of the adaptive immune system
Evasion strategies help pathogens persist despite host immune response.
Virulence Factor: Infection
Factors that establish and maintain disease once the pathogen has invaded.
Key Types
1. Exoenzymes: degrade host barriers and spread infection
2. Toxins: disrupt host cell function
- Exotoxins: secreted, specific action (e.g., neurotoxins)
- Endotoxins: part of Gram-negative cell wall (e.g., LPS) → cause inflammation
Infection factors are responsible for clinical signs and disease progression.
Bacillus anthracis exoenzyme
phospholipase
Dissolves membranes of phagosomes and host cells, preventing antigen processing and MHC I presentation.
→ Helps bacteria survive within host cells (immune evasion).
Clostridium perfringens exoenzyme
Collagenase
Breaks down collagen in connective tissue → enables rapid tissue penetration.
→ Major factor in gas gangrene (necrotizing soft tissue infection).
→ Facilitates invasion and spread.
Helicobacter pylori exoenzyme
Urease
Neutralizes stomach acid by producing ammonia → allows survival in the gastric mucosa.
Also dissolves protective mucus, exposing epithelium to damage.
→ Promotes invasion and ulcer formation.
Staphylococcus aureus exoenzyme
-
Coagulase
Induces clot formation around the bacteria using host fibrin → shields pathogen from immune attack.
→ Allows immune evasion and persistence in tissue or blood. -
Hyaluronidase
Breaks down hyaluronic acid, a component of connective tissue matrix.
→ Loosens intercellular junctions, facilitating deep tissue invasion. -
DNase
Degrades DNA in neutrophil extracellular traps (NETs), which are released to trap pathogens.
→ Enables bacteria to evade neutrophil defenses and continue spreadin
Toxins
Naturally occurring substances that cause harm or disease, produced by various organisms.
- Most are proteins
- Categorized by location relative to cell, structure, or mechanism of action
Types
1. Endotoxin: lipid A portion of LPS in Gram-negative bacteria; released when bacteria die
2. Exotoxins (secreted proteins):
- A-B toxins: A = active portion, B = binding portion
- Membrane-disrupting toxins: form pores or degrade membranes
- Superantigens: overstimulate immune system → cytokine storm
Toxins are key virulence factors that directly damage host cells or dysregulate immune responses.
Endotoxin (Lipid A of LPS)
A non-protein toxin found in the outer membrane of Gram-negative bacteria.
→ Specifically the Lipid A portion of lipopolysaccharide (LPS)
Key Features
- Low toxicity compared to exotoxins; requires high dose (≥ 6 mg/kg)
- No specific host target → causes harm by overstimulating immune system
- At low concentrations: no symptoms
- At high concentrations: triggers cytokine storm
Clinical Effects
1. Septicemia: bacteria in blood releasing endotoxin
2. Overwhelming immune response → cytokine storm
- Shock: critically low blood pressure → ↓ tissue perfusion and ↓ oxygenation
- Organ failure: secondary to poor oxygen delivery
Note: Some antibiotics that lyse Gram-negative bacteria can worsen shock by releasing large amounts of LPS.
Exotoxins
Secreted proteins produced by Gram-positive, Gram-negative, and some fungi or other microbes.
→ Often the most toxic substances known (nanogram-level lethality)
Examples
- Botulinum toxin: 2 ng/kg (causes flaccid paralysis)
- Tetanus toxin (tetanospasmin): 3 ng/kg (causes spastic paralysis)
Types of Exotoxins
1. Intracellular targeting toxins: enter host cells and disrupt key functions
2. Membrane-disrupting toxins: form pores or degrade membrane lipids
3. Superantigens: non-specifically activate T cells → cytokine storm
Exotoxins damage host cells directly, and their extreme potency contributes to severe disease symptoms.
Intracellular Targeting Toxins
Toxins that bind to and enter host cells, disrupting intracellular function.
- A-B toxins are a major subclass of intracellular targeting toxins, but not all such toxins follow the A-B model.
- A subunit = Active portion → exerts toxic effect
- B subunit = Binding portion → attaches to specific host receptor
- Entry often requires cleaving/separation of A and B
Key Feature:
- Antibodies that block the B subunit can prevent toxin entry and neutralize the toxin.
A-B toxins are the most well-characterized intracellular toxins, but some others may use different mechanisms of cell entry or activity.
Clostridium botulinum AB Toxin
Botulinum Toxin
infection
A neurotoxin that blocks acetylcholine release at neuromuscular junctions → causes flaccid paralysis.
- Most toxic substance known by weight
- Leads to respiratory failure if untreated
- Toxin-mediated during **infection
Causes
1. Foodborne: toxin ingested from improperly preserved foods
2. Wound: spores germinate in anaerobic wounds
3. Infant botulism: spore ingestion (e.g., in honey) → colonization and in vivo toxin production
symptoms
1. difficulty swallowing
2. muscle weakness
3. double vision, blurry vision
4. drooping eyelids
5. difficulty moving the eyes
6. slurred speech
7. difficulty breathing
