Microbial Genetics & Recombinant DNA – Exam Review
Replica Plating Techniques
- Master plate stamped onto two media via sterile velvet
- Antibiotic-supplemented plate → colonies that grow are antibiotic-resistant mutants
- Histidine-supplemented vs. histidine-lacking plates → growth only on supplemented plate identifies a histidine auxotroph (nutritional mutant)
Ames Test (Mutagen/Carcinogen Screen)
- Uses a histidine auxotroph of Salmonella
- Mix: auxotroph + suspected mutagen + rat-liver extract
- Plate on medium lacking histidine
- Revertant colonies (His⁺ prototrophs) indicate mutagenic potential; ↑ revertants ⇒ suspected carcinogen
Horizontal Gene Transfer (HGT)
- HGT introduces foreign DNA without reproduction; 3 major mechanisms:
- Transformation: uptake of naked DNA; success depends on cell competence & homologous recombination (chromosomal) or plasmid uptake
- Conjugation: plasmid copy transferred through type IV pilus/mating bridge; key driver of antibiotic resistance
- Transduction: bacteriophage-mediated DNA transfer
• Generalized (lytic phage packages random host DNA)
• Specialized (lysogenic phage excises with adjacent host genes via integrase)
Plasmid Basics
- Extrachromosomal, self-replicating DNA; often carry fertility genes (pilus), promoters & selectable traits
- Clinically relevant genes: antibiotic resistance, antibiotic synthesis, virulence factors, toxin genes
- Plasmid incompatibility: competing plasmids with same promoter; one silences the other ⇒ potential therapeutic approach to suppress resistance
- Amplify gene of interest (GOI) via PCR (heat-stable polymerase e.g., Taq)
- Cut GOI & cloning vector with same restriction enzyme (e.g., EcoRI) → compatible sticky ends
- Ligate to form recombinant plasmid
- Introduce plasmid into competent bacteria (chemical or electroporation transformation)
Selection & Screening
- Plate on medium containing antibiotic → only cells with any plasmid survive
- Blue-white screen (lacZ disruption)
• Blue colonies: non-recombinant plasmid (lacZ intact)
• White colonies: recombinant plasmid (lacZ disrupted by GOI)
Plant Genetic Engineering (Ti Plasmid)
- Agrobacterium tumefaciens Ti plasmid delivers insert into plant chromosome
- Stable integration (crop improvement) or transient expression (rapid protein production)
- Traits engineered: stress tolerance (drought/heat), pest resistance, yield or nutrient enhancement, therapeutic protein production
Key Applications of Recombinant DNA
- Gene therapy (e.g., sickle-cell disease), molecular diagnostics
- Recombinant microbes: industrial enzymes, vaccines, biopharmaceuticals (insulin), bioremediation
- Transgenic plants: hardier food crops, edible vaccines, specialty metabolites
- Transgenic animals:
• Aquaculture (rapid-growing salmon)
• Pharming (therapeutic proteins in milk/eggs)
• Humanized disease models (immune-system or organ replacement genes)
• Xenografting: gene-edited pig organs with human antigens for transplantation