Overview
This lecture covers the principles of microbial pathogenesis, how scientists study pathogens, and a detailed case study focusing on Staphylococcus aureus, especially its methicillin-resistant form (MRSA). Key concepts include infection steps, pathogen evasion tactics, and the genetic evolution of MRSA.
General Principles of Pathogen Infection
- Pathogen infection involves encounter, entry, establishment, damage, and transmission.
- Entry routes include respiratory, oral, sexual, insect-borne, and wounds (e.g., staph enters through skin cuts).
- Virulence, inoculum size, and host immune status influence infection success.
- Disease occurs when a microbe causes host damage, either by toxins or immune response.
Methods for Studying Pathogens
- Disk diffusion (antimicrobial susceptibility test) assesses bacteria's resistance to antibiotics.
- Pulsed-field gel electrophoresis distinguishes bacterial strains during outbreak investigations.
- Model systems (animal/cell cultures) help study disease mechanisms; human studies are limited.
- Koch’s postulates establish causation between a microbe and disease.
- LD50 (lethal dose 50) and ID50 (infectious dose 50) quantify microbe virulence.
Staphylococcus aureus and MRSA
- S. aureus: Gram-positive, non-motile, grape-like clusters, facultative anaerobe, survives on skin/nasal passages.
- Skin is aerobic, dry, acidic, and nutrient-poor; staph adapts using various metabolic pathways.
- About 1/3 of people carry S. aureus in their noses at any time.
Pathogenesis and Host Response
- Staph enters through skin breaches, causing immune response (notably via neutrophils).
- Neutrophils attack with reactive oxygen species (ROS); staph counters with antioxidants and catalase.
- Staph secretes toxins (e.g., Panton-Valentine leukocidin) that kill neutrophils.
- Abscesses form as host walls off bacteria with fibrin; staph produces coagulase to enhance this, making treatment difficult.
- Host attempts to restrict bacterial growth by limiting iron (nutritional immunity), but staph uses siderophores and hemolysins to acquire iron.
Evolution and Genetics of MRSA
- S. aureus developed penicillin resistance by acquiring beta-lactamase, which destroys penicillin's beta-lactam ring.
- Methicillin was created to bypass beta-lactamase, but MRSA arose by acquiring the mecA gene (alternate transpeptidase).
- MRSA USA300, a prevalent strain, gained additional genes: Panton-Valentine leukocidin (PVL) and the ACME cluster (from S. epidermidis), enabling survival on skin and community transmission.
Key Terms & Definitions
- Abscess — a pus-filled nodule caused by immune response to infection.
- Disk diffusion test — a method to assess bacterial resistance to antibiotics via growth inhibition zones.
- Pulsed-field gel electrophoresis — technique to differentiate strains by DNA fragment patterns.
- Koch’s postulates — criteria to prove a microbe causes a specific disease.
- LD50/ID50 — quantities of a pathogen needed to kill/infect 50% of test subjects.
- Siderophores — molecules secreted by bacteria to capture iron from the environment.
- Coagulase — staph enzyme that promotes fibrin formation, aiding abscess development.
- mecA gene — encodes methicillin-resistant transpeptidase in MRSA.
- PVL (Panton-Valentine leukocidin) — toxin killing neutrophils, increasing virulence.
- ACME — gene cluster aiding survival on acidic skin, acquired from S. epidermidis.
Action Items / Next Steps
- Review textbook Figures 23.1, 23.3, 23.4, 23.6, 23.8, 23.9, 23.10, and 23.11 for visuals of processes discussed.
- Read about Koch’s postulates, LD50/ID50, and mechanisms of antibiotic resistance.
- Practice applying infection steps and mechanisms to new pathogens for exam prep.