Lessons 8-12 Flashcards
Penicillin
Discovered by Alexander Fleming in 1929, developed by Howard Florey and Ernst Chain.
β-lactam ring, produced by actinomycetes
bactericidal antibiotic
bacteriostatic antibiotic examples
clindamycin, tetracyclines
Testing antibiotic efficacy
MIC - minimal inhibitory concentration.
Determined by E-test, gradient of antibiotic in paper-strip
Strain sensitivity to multiple antibiotics tested with Kirby-Bauer disk susceptibility test.
Targets of antibiotic action
- Cell wall synthesis: Vancomycin, bacitracin, cycloserine, penicillin
- Cell membrane: gramicidin, patenmycidin
- DNA gyrase: quinolones
- DNA-directed RNA polymerase
- 30s inhibitors: tetracyclines
- 50s inhibitors: chloramphenicol
- tRNA inhibitors
- Folic acid metabolism: sulfa drugs
Cell wall inhibiting antibiotics
Vancomycin - binds ends of peptides, prevents crosslink formation
Penicillin, Cephalosporins (β-lactam ring) blocks enzyme involved in cross linking
Cycloserine - blocks formation of peptide for crosslink (blocks D-Ala-D-Ala synthesis)
Bacitracin - blocks movement of Bactoprenol across membrane
Sulfa drugs
Analogue for vitamin B9 precursor, block Folic acid formation, humans are safe from antibiotic because folic acid is supplied through the diet.
Rifampin
blocks bacterial RNA polymerase
Gramicidin & Plantemycin
Antibiotics that target the cell membrane
G: Forms Cation channel in membrane, bacteria cannot maintain PMF
P: Blocks bacterial fatty acid synthesis
Mechanisms of Antibiotic resistance
Reduced uptake into cell - chloramphenicol
Active efflux from cell - tetracycline, multi drug resistance exporter
Eliminating or reducing binding to target - β-lactams
Enzymatic cleavage or modification to inactivate antibiotic molecule - β-lactams, chloramphenicol, add post-translational modification to aminoglycosides, so they can no longer interact with ribosome
Metabolic bypass of blocked reaction
Overproduction of antibiotic target
Bacterial drug responses
susceptible, tolerant, or persistent
iChip
Allows the “culturing” of uncultured soil microbes by growing them in a plate exposed to soil
Teixobactin
Antibiotic against gram + bacteria, produced by Eleftheria terrae, which inhibits cell wall synthesis by binding to cell wall precursors Lipid I and Lipid II. Low susceptibility to resistance because the target does not exist in the producing cell and the target is highly conserved among eubacteria. It cannot penetrate the outer membrane of frame negative bacteria
Its biosynthetic gene cluster encodes two large, non-ribosomal peptide synthetase-coding genes.
It’s structure contains D-amino acids, methylphenylalanine
Why do antibiotic resistances occur frequently?
- Heterogeneous population (subpopulation selection)
- HGT from species that are already resistant (exposed to natural antibiotic in their niche, or from the antibiotic producing organism itself)
- industrial application of antibiotics encourage positive selection by exposing a large number of bacterial to frequently sublethal doses of antibiotics, conferring a competitive advantage to resistant strains.
Fungi as pathogens
- Candidiasis is caused by the Candida fungi. Most common is Candida albicans. Symptoms vary with area of the body: mouth/throat = thrush, vagina = yeast infection
- Aspergillosis is found in soil, on plants, and in decaying organic matter. Infection by inhalation of spores -> conidial germination
Examples of antifungal agents
Clotrimazole - Inhibition of sterol synthesis
Griseofulvin - Disrupts mitotic spindle
Amphotericin B - Binds to sterols -> membrane integrity destroyed
Nystatin - Forms pores in membranes
Helminths
- Roundworms (Nematodes)
- Tapeworms (Cestodes)
- Flukes (Trematodes)
Nematodes
Possess digestive, nervous, excretory, and reproductive systems. No discrete circulatory or respiratory system.
Example 1: Ascaris lumbricoides
Example 2: Filariasis. Nematodes inhabit the lymphatics -> elephantiasis, river blindness. Intermediate host: mosquito
Cestodes
Flattened, elongated, segments called proglottids. No alimentary canal -> substances must enter the worm across the tegument. Generally inhabit the intestinal lumen. Contracted from raw or undercooked infected meat.
Trematodes
Flattened leaf-shaped bodies. Some contracted from contaminated water, penetrate skin, some from algae.
Example: Schistomiasis. Complex life cycle. Adults mate in host gut, eggs passed fecally. Eggs hatch, and young grow in snail.
Phylum apicomplexa
Protozoa, obligate intracellular parasites. Have apical complex - secretory organelles (micronemes + rhoptries). Have apicoplast.
Ex: malaria, genus Plasmodium
Malaria
Genus plasmodium. Fever, splenomegaly, headache and vomiting. Paroxysms every third day.
Measures to combat: bed net with insecticide, indoor residual spraying, spatial planning, region-specific anti-malarials