Mechanisms of Genetic Variation and Gene Regulation

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Bacterial Pathogenesis

• Pedestal formation process involves two stages: pEAF (EPEC attaching and effacing factor) and T3SS (type 3 secretion system) with intimin.
• Invasion and dissemination occur through zipper mechanism in Listeria monocytogenes and trigger mechanism in Shigella flexneri.

Intracellular Pathogens

• Advantages of intracellular pathogens include evasion of immune system, prolonged infection, and access to host nutrients.
• Disadvantages include intracellular killing, limited nutrient availability, and immune detection.
• Non-phagocytic vs phagocytic invasion: Listeria and Shigella use actin-mediated motility.

Metal Ion Acquisition

• Structural and functional cofactors: manganese, iron, copper, zinc.
• Nutritional immunity: metal ion acquisition strategies used by bacteria to evade host defenses.
• Functions of metal ions:
  • Manganese: enzyme cofactor, antioxidant.
  • Iron: electron transport, enzyme cofactor.
  • Copper: electron transport, enzyme cofactor.
  • Zinc: enzyme cofactor, protein structure.

Immune Evasion Strategies

• Immune receptors: avoid detection by immune cells.
• H. pylori avoids detection by: complement, immune cells, and host mimicry.
• Complement: function, C3a, C5a, and membrane attack complex.
• Avoiding complement: MBL (mannose-binding lectin), immune cells, and capsule.

Vaccination

• What makes a vaccine effective: generating T cell immunity, activation of B cells and antibodies, and T-dependent responses.
• LAVs (live attenuated vaccines), methods of attenuation, risks, and weaknesses.
• Toxoid vaccines, purification, response, risks, and weaknesses.
• Conjugate vaccines, vaccinating populations, and antigenic variants.

Antibiotics

• Types of antibiotics: cell wall targeting, ribosome targeting, and others.
• Ideal antibiotics: broad-spectrum, narrow-spectrum, and classification.
• Mechanisms and specificity:
  • Transpeptidase: beta-lactams.
  • Ribosome targeting: tetracyclines, aminoglycosides, and macrolides.
  • Cell wall targeting: glycopeptides.

Antibiotic Resistance

• Causes: genetic basis, intrinsic, acquired, and history.
• Resistance mechanisms:
  • Efflux pumps: tetracycline resistance.
  • Inactivation: beta-lactamases.
  • Target modification: methicillin resistance.
  • Mobile genetic elements (MGEs).

Phage Therapy

• Pros and cons: alternative to traditional antibiotics.
• New antibiotics: phenotypic screening, target-based screening, and library screening.

MRSA, VRE, and Acinetobacter baumanii

• Characteristics, infections, transmission, virulence factors, and genomics of each.
• MRSA: mecA gene, PBP2a, and pan-genome.
• VRE: Enterococcus faecium, catalase-negative, gamma-haemolytic, and gelE, sagA, Cyl, Hylfm.

Pseudomonas aeruginosa

• Characteristics, genomics, disease, diagnosis, treatment, and symptom management.
• CFTR (cystic fibrosis transmembrane conductance regulator) modular combinations.

Genomics

• Sanger sequencing, sequencing by synthesis, and annotation of genomes using BLAST.
• Advantages vs disadvantages of using Illumina vs Nanopore.

Secretion Systems

• Sec translocase, twin arginine transport, and type 1, 3, 4, 5, 6, 7 secretion systems.
• Autotransporter pathways and OMVs (outer membrane vesicles).

Identifying Pathogens

• Culture tests, molecular testing, immunoassays, nucleic acid amplification, and Baird Parker agar.
• EMB agar, biochemical tests, automated culture systems, and culture-independent tests.

CRISPR

• History, function, and defence against bacteriophages.
• Crispr-cas systems, stages of CRISPR immunity, and DAM (DNA-directed RNA polymerase).

Adherence and Colonisation

• Pili and fimbrial adhesion: gram-positive and gram-negative.
• Chaperone-usher pili, type IV pili, and gram-positive pili.
• Sortase, afimbrial adhesins, and TAAs (type 5 secretion adhesins).

Bacterial Toxins

• Major toxin types: endotoxins, exotoxins, pore-forming toxins, and phospholipases.
• Endotoxins: trigger cytokine release.
• Exotoxins: classifications, AB toxins, and non-protein AB toxins.

Clostridial Diseases

• Clostridium genus, characteristics, and diseases.
• C.difficile, C.perfringes, and Clostridial myonecrosis.
• Alpha toxin, phospholipase A activity, and CPE (clostridial food poisoning).

Chlamydia

• Characteristics, disease, consequences, and life cycle.
• Genomics, diagnostics, and treatment.

Syphilis

• Disease course, primary syphilis, secondary syphilis, and tertiary syphilis.
• Vertical transmission, epidemiology, and treponea palladium characteristics.
• Immune evasion, transmission, and subspecies.

Campylobacter

• History, characteristics, infectious dose, and pathogenesis.
• Flagella, replication, cytokines, and nuclease toxin.

Helicobacter pylori

• Characteristics, disease, clinical manifestations, and virulence factors.
• Urease, adhesins, LPS, flagellin, and BabA.

Shigella

• Subgroups, E. coli biotype, shigellosis, transmission, and treatment.
• Pathogenesis, M cells, pro-inflammatory responses, and intracellular lifestyle.

Salmonella

• Ancestry, serovars, enteric fever, and S. typhi.
• Incubation period, pathogenicity islands, and virulence factors.

Tuberculosis

• Mycobacterium, identification, stain acid-fast, and unusual cell wall.
• Lipids, M. tuberculosis, life cycle, and virulence factors.
• Pathogenesis, extrapulmonary TB, and epidemiology.

Mycobacterium leprae

• Leprosy, epidemiology, pathogenesis, and treatment.
• Growth and culture, evolution, and genomics.

Atypical Mycobacteria

• Pulmonary NTM infections, MAC, M. abcessus, and disease.
• Treatment, biofilms, and cutaneous NTM.

Anti-Mycobacterials

• Isoniazid, ethambutol, pyrazinamide, and new antibiotics.
• Bedaquiline, delaminid, and telacebec.

Streptococcus pneumoniae

• Pneumococcus, cell wall, history, and genome.
• Characteristics, carriage, disease, and global burden of disease.
• Virulence factors, capsule, serotype, and serotype 1.

Gonorrhoea

• Characteristics, host adaptation, genomics, and transmission.
• Tropism, colonisation, adhesins, and type 4 pili.
• Evasion of immune system, phase variation, and antigenic variation.

Group A Streptococcus

• Importance, characteristics, transmission, and epidemiology.
• Classification, group A, carbohydrates, and catalase negative.
• Antibiotic resistance, S. pyogenes, and infections.

Burkholderia species complex

• Genomics, history, B. pseudomallei complex, and disease.
• Epidemiology, diagnosis, B. cepacia, and mortality in cystic fibrosis.
• Cepacia syndrome, lung function, and necrotising pneumonia.

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