Overview
This lecture covers intracellular pathogens, focusing on Listeria monocytogenes and Mycobacterium tuberculosis (TB), their infection mechanisms, and challenges in treating diseases they cause.
Listeria monocytogenes
- Gram-positive, motile rod bacteria with versatile metabolism; grows in both oxygen-rich and low oxygen environments.
- Can grow at refrigerator temperatures (as low as 2°C) allowing proliferation in cold-stored food.
- Ubiquitous in nature—found in soil, water, and various hosts.
- Infection via contaminated food; causes mild GI symptoms but can cross placenta in pregnant women, leading to fetal death.
- Invades non-phagocytic cells by inducing phagocytosis, escapes phagosomes using Listeriolysin O (LLO).
- Uses ActA protein to polymerize host actin, moving within and between cells to evade immune detection.
- Virulence genes llo and actA are regulated by transcription factor PrfA, activated inside host cells.
- Two types of food poisoning: infection (bacterial growth in body, slower onset, treat with antibiotics) vs. intoxication (pre-formed toxin ingestion, rapid onset, no antibiotics).
Staphylococcus aureus Food Poisoning
- S. aureus can grow in improperly cooled food, producing heat-stable toxins (enterotoxins) that cause rapid-onset vomiting/diarrhea.
- Toxin ingestion results in symptoms within hours; bacteria do not multiply in the host.
- Epidemiology: outbreaks often traced to contamination by handlers, insufficient cooling of food enables bacterial growth and toxin production.
Mycobacterium tuberculosis (TB)
- Acid-fast, Gram-positive, non-motile bacteria with mycolic acid and capsule, making it drug-resistant.
- Spread by inhalation of droplets from infected individuals; enters lungs and is phagocytosed by macrophages.
- TB blocks phagosome-lysosome fusion, allowing survival inside macrophages.
- Leads to granuloma formation (walled-off infection site); bacteria may remain dormant for years.
- Primary TB is mild, often self-limiting; secondary TB occurs if immunity weakens, bacteria escape granuloma, causing severe disease and transmission.
- Tuberculin skin test (PPD) is used to detect exposure or latent infection.
- Treatment requires prolonged, multi-drug antibiotic therapy; public health control relies on screening and monitoring in the US.
- Vaccination not used in US to preserve skin test utility.
Intracellular Pathogens: Challenges & Immunity
- Intracellular pathogens evade or tolerate lysosomal destruction (by escaping, blocking fusion, or surviving within).
- Immune response: Antibodies and phagocytes can't reach pathogens inside cells; cytotoxic T cells detect infected cells via displayed peptides and destroy them.
- Antibiotic efficacy is reduced due to difficulty in penetrating multiple membranes to reach intracellular bacteria.
Key Terms & Definitions
- Intracellular pathogen — a microbe that lives and replicates inside host cells.
- Listeriolysin O (LLO) — a pore-forming toxin allowing Listeria escape from phagosomes.
- ActA — a protein used by Listeria to polymerize actin and move intracellularly.
- PrfA — a transcriptional activator regulating Listeria virulence genes.
- Granuloma — a walled-off structure formed by immune cells to contain infection.
- Phagosome — a membrane-bound compartment that engulfs pathogens in cells.
- Tuberculin skin test (PPD test) — diagnostic injection to check for prior TB exposure by skin reaction.
- Cytotoxic T cell (CD8+) — immune cell that kills infected cells displaying foreign antigens.
Action Items / Next Steps
- Review current Listeria and foodborne outbreak data (check notes for provided link).
- Watch recommended video on Listeria actin-based motility (Figure 24.2).
- Complete assigned readings on intracellular pathogen immune evasion mechanisms.