Lessons 8-12 Flashcards

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1
Q

Penicillin

A

Discovered by Alexander Fleming in 1929, developed by Howard Florey and Ernst Chain.

β-lactam ring, produced by actinomycetes
bactericidal antibiotic

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2
Q

bacteriostatic antibiotic examples

A

clindamycin, tetracyclines

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3
Q

Testing antibiotic efficacy

A

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.

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4
Q

Targets of antibiotic action

A
  1. Cell wall synthesis: Vancomycin, bacitracin, cycloserine, penicillin
  2. Cell membrane: gramicidin, patenmycidin
  3. DNA gyrase: quinolones
  4. DNA-directed RNA polymerase
  5. 30s inhibitors: tetracyclines
  6. 50s inhibitors: chloramphenicol
  7. tRNA inhibitors
  8. Folic acid metabolism: sulfa drugs
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5
Q

Cell wall inhibiting antibiotics

A

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

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6
Q

Sulfa drugs

A

Analogue for vitamin B9 precursor, block Folic acid formation, humans are safe from antibiotic because folic acid is supplied through the diet.

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7
Q

Rifampin

A

blocks bacterial RNA polymerase

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8
Q

Gramicidin & Plantemycin

A

Antibiotics that target the cell membrane
G: Forms Cation channel in membrane, bacteria cannot maintain PMF

P: Blocks bacterial fatty acid synthesis

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9
Q

Mechanisms of Antibiotic resistance

A

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

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10
Q

Bacterial drug responses

A

susceptible, tolerant, or persistent

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11
Q

iChip

A

Allows the “culturing” of uncultured soil microbes by growing them in a plate exposed to soil

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12
Q

Teixobactin

A

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

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13
Q

Why do antibiotic resistances occur frequently?

A
  • 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.
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14
Q

Fungi as pathogens

A
  • 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
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15
Q

Examples of antifungal agents

A

Clotrimazole - Inhibition of sterol synthesis
Griseofulvin - Disrupts mitotic spindle
Amphotericin B - Binds to sterols -> membrane integrity destroyed
Nystatin - Forms pores in membranes

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16
Q

Helminths

A
  1. Roundworms (Nematodes)
  2. Tapeworms (Cestodes)
  3. Flukes (Trematodes)
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17
Q

Nematodes

A

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

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18
Q

Cestodes

A

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.

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19
Q

Trematodes

A

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.

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20
Q

Phylum apicomplexa

A

Protozoa, obligate intracellular parasites. Have apical complex - secretory organelles (micronemes + rhoptries). Have apicoplast.

Ex: malaria, genus Plasmodium

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21
Q

Malaria

A

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

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22
Q

Toxoplasmosis

A

Caused by Toxoplasma gondii - ~1/3 of humans infected. Often few or no symptoms. Infection during pregnancy can lead to spontaneous abortion or severely handicapped baby.

Life cycle: Resides in cat intestines -> mice -> cats. T. gondii in cat feces can also be ingested by humans or contaminated food, or it can be ingested by sheep and pigs and then eaten undercooked by humans.

23
Q

Phylum Kinetoplastida

A
  • Flagellated protists. Presence of kiteoplast: disk of interlocking DNA circles - adjacent to the organism’s flagellar basal body. Transmitted by insects.
  • Example: Trypanosoma Bruce -> African sleeping sickness. Fever, headache, muscle / joint aches, neurological problems.
24
Q

Rhizoxin

A

16-membered lactone ring, connected to oxazole ring by unsaturated chain. Synthesized by polyketide synthase.

Causative agent of rice seedling blight (abnormal swelling of the seedling roots), produced by Burkholderia facultative endosymbiont in Rhizopus microsporus. Binds to rice β-tubulin, arresting mitosis and the cell cycle.

25
Q

Live/Dead staining

A

One dye stains all cells, while the other stains only DNA, which is accessible only in dead cells.

26
Q

Diarrhea

A
  • > 3 liquid stools / day. Acute watery, bloody (dysentery), or persistent (>14 days).
  • Preventable & Treatable.
  • 2B cases /year, 2nd leading cause of death in children < 2yo. , kills 1.5M children/yr.
  • Prev: hygiene, fresh water, sanitation, promote breastfeeding, supplement zinc, and Vitamin A for immune function.
  • Treatment: Oral RH therapy + Zn + continued feeding.
27
Q

GI barrier

A
  • stomach: lots of mucus, few bacteria.
  • small intestine: thinner mucus, microvilli, mucin
  • large intestine: thicker mucus, much more bacteria.
28
Q

Dynamicity of GI barrier

A

Response to pathogen: mucus production, modulation of inflammatory and apoptotic pathways, shedding mucins, secretion of antimicrobials and pathogen-specific immunoglobulins.

Pathogens subvert mucus barrier by avoiding mucus (M cells), disturbing tight junctions and mucus production, and degrading mucus.

29
Q

Giardiasis

A

Protozoal, caused by Ghiardia intestinalis

food and water-borne, p2p spread. Not common in developed world but very common in developing world. Classic symtpoms: d, v. Gas, greasy stools, cramps

30
Q

Secretory Diarrhea

A

Form of Gastroenteritis

No/low fever or wb cells in stool

V. cholerae, ETEC, EPEC, EHEC
Bacteria remain outside of epithelial cells

31
Q

Inflammatory Diarrhea

A

Form of Gastroenteritis

Fever, wb cells in stool

C. jejuni, Shigella, Non-typhoidal Salmonella, EIEC
Invasion of epithelial mucosa, block host protein synthesis, damage endothelia (capillary damage, blood loss)

32
Q

Enteric Fever

A

Febrile Patient

High fever, wb cells in stool

Typhoidal salmonella, Enteropathogenic Yersinia

33
Q

Non-Typhoidal Salmonella

A

Food-borne, 3M deaths / year

Usually not systemic, mortality very low in developed countries. Found in humans and animals.
Salmonella’s T3SS encoded on SPI-1/2

SPI-1 for extracellular use. SPI-2 acts from within vacuole

34
Q

Typhoidal Salmonella

A

Human-only, systemic infection, p2p spread, carrier state (Typhoid Mary)

Typhoid fever: f, m, h, d, rose-colored spots on chest, enlarged liver & spleen

Capsular polysaccharide (Vi antigen)

35
Q

Pneumonia

A

Leading cause of death in children worldwide.

Preventable with immunization, adequate nutrition, and addressing environmental factors. Pneumonia caused by bacteria can be treated with antibiotics.

Symptoms: rapid, difficult breathing, cough, f, loss of appetite

Causes: S. pneumoniae, Haemophilus influenzae type B, Respiratory syncytial virus, B. pertussis, Measles v., Influenza A

Prev: Vaccine against flu, measles, S. peumoniae, B. pertussis. Adequate nutrition, reducing indoor air pollution, and increasing hygiene.

36
Q

Models of Cholera infection

A

Suckling mice: readily colonized, useful for ID of colonization factors, do not develop cholera gravis

Rabbit Ligated Ileal loops: Useful for enterotoxicity, used in studies of V. Cholera attachment and gene expression in vivo, but requires surgery, and bypasses natural route of infection and normal gut physiology (peristalsis)

Infant rabbit + Cimetidine: best of both worlds.

37
Q

Gain of Function Research

A

Goal: identify combinations of mutations that could allow an animal virus to jump to unprepared humans, and anticipate those that could become dangerous, but increase the risk of accidental release and exposure. In addition, publication of results can help bioterrorists.

38
Q

Bioterrorism Category A

A

Biological threats with serious potential for harm

  • Anthrax
  • Plague
  • Smallpox
  • Tularemia
39
Q

Bioterrorism Category B

A

Moderate agents with low potential for harm - moderately easy to disseminate, moderate morbidity, low mortality

  • Food & water safety threats, toxins from pathogens
40
Q

Bioterrorism Category C

A

Engineered agents that can be mass produced and have high potential for damage - future threats

41
Q

Anthrax

A

Bacillus anthraces - forms spores, does not spread from person to person

3 types: cutaneous, gastrointestinal, respiratory.
Cutaneous: Blisters -> ulcers. 20% mort. without antibiotic treatment.
Gastrointestinal: Flu-like -> severe v, d, abd. pain. 25-60% mort.
Respiratory: mild f, sore throat -> cough, chest discomfort, shortness of breath, aches 75% mortality.

42
Q

Tularemia

A
Francisella tularensis ("rabbit fever")
V. low infectious dose (10 bacteria) 
Symptoms: skin ulcers, sore throat, mouth sores, diarrhea, pneumonia, fever, chills, headache, muscle aches, joint pain, -> difficulty breathing, respiratory failure.
43
Q

High Pathogenicity vs. Low Pathogenicity Avian Flu

A

HPAI thought to arise in poultry after domesticated birds become infected by LPAI from wild-bird reservoir. Switch happens when basic amino acid residues are introduced into the HA0 cleavage site, allowing HA to be cleaved by ubiquitously expressed host proteases. Easier cleavage -> easier replication -> More pathogenic.

Major pandemics thus far caused by genetic mixing between human and animal influenza viruses.

44
Q

Genetic modifications to make flu more infectious

A
  • Increased virus production in Upper respiratory tract, efficient release of virus particles from respiratory tract.
  • Mutations allowing viral polymerase to function at 33º (human URT temp) instead of 41º (bird intestinal tract).
45
Q

Categories of symbiosis

A
  • Commensalism, Mutualism, Parasitism.
  • Ectosymbiosis, Endosymbiosis
  • Facultative, Obligatory
  • Horizontally, Vertically transmitted.
46
Q

Cyanobacteria

A

Photoautotrophs with plant like oxygen-generating photosynthesis. Form filamentous colonies, where some cells differentiate into nitrogen fixating heterocytes.
Chloroplast likely evolved from endosymbiotic cyanobacterium.

47
Q

Endosymbiosis in Eukaryotic Evolution

A
  • Mitochondria evolved by endosymbiosis of an aerobic prokaryote.
  • Plastids evolved by endosymbiosis of a photosynthetic cyanobacterium. -> red and green algae.
  • Red and green algae underwent secondary endosymbiosis, were ingested by a heterotrophic eukaryote.
48
Q

Symbiotic interactions with Fungi

A

Eukaryotes with heterotrophic, absorptive nutrition and chitinous cell walls.
Symbiotic fungi receive energy directly from a plant or algal partner

Examples: Lichens, provide structure, anchoring, and shelter to symbiotic algae, who provide glucose.
 Mycchorizal fungi (plant roots) provide extended access to mineral nutrients and water access. Acquire nutrients normally not accessible to plants, who provide glucose in exchange.
49
Q

Models for studying host-microbe interactions

A

Binary - squid light organ.

Simple Consortia - insect gut, leech gut.

50
Q

E. scolopes & V. fischeri

A

Exchange carbs, AAs, Lipids, & O2 for light (E. scolopes is a nocturnal animal)

Part of chemical communication is MAMPs: normally LPS provokes a proinflammatory response and PGN causes death of epithelial cells. Has beneficial effect in creating symbiosis. In mammals, LPS is essential for gut homeostasis. In E. scolopes, MAMPs specific to V. fischeri induce morphogenesis

V. fischeri are selected by surviving NO-containing vesicles and antimicrobial cocktail present in acidic mucus. Primed to follow chitobiose gradient through pores into crypts by exposure to chitobiose.

51
Q

Insect Symbiosis

A

Endosymbionts ubiquitous in insects, vertical transmission, often uncultivable.
Often very small genome (life in insulation + elimination of redundant genome)
Obligate symbionts coevolve. Many provide essential nutrients for hosts that feed nutrient-poor diets (blood, sap)

Example: mealybug. composite of 6 genomes! Endosymbiont Tremblaya, which has another symbiont Moranella. Also has exogenous sequences from at least 3 different bacterial species.

Facultative endosymbionts: vertical transmission over ecological timescales, horizontal transmission over evolutionary timescales. May be reproductive manipulators (male killing or cytoplasmic incompatibility) or mutualists.

Example: presence of Wolbachia increases protection against Drosophila C virus. Wolbachia also necessary for nematodes development and viability. Killing wolbachia with antibiotics can treat filariasis. Causes cytoplasmic incompatibility in mosquitos (could control Dengue)

52
Q

Human gut microbiota

A

10 Trillion cells. 70% not yet cultured. Crosstalk with immune, neural, and endocrine functions. Important in nutrition, host energy and metabolism, epithelial proliferation, gut maturation, inflammatory immune responses, pathogen resistance.
Mutualistic association derived from a long co-evolution.
Microbiome can be modulated.

Disruption of ecological balance can lead to infection, and disruption of tolerance can lead to auto-immunity and inflammatory disorders.

Only 4 phyla dominate human-associated microbiota. Sequencing more gut microbiota is leading to more rare genes, but number of common genes is constant -> most useful clinically.

53
Q

Dysbiosis

A

Germ-free rodents require 30% more calories, due to incomplete digestions.

Transplantation of microbiome from obese mice can induce obesity.
Individuals with lower genetic diversity in microbiome have less healthy inflammatory and metabolic traits. Affected by repeated antibiotic therapy, nutritional transition to more processed diets, hygienic environments?

Vicious cycle: modulation of gut microbiota, low-grade inflammation. Can only be broken by combined modulation of microbiota and inflammation.

54
Q

Ideal probiotics for humans and animals

A
  • adhere to intestinal mucosa
  • easily cultivated
  • remain viable for a long time.
  • Withstand acidity from the stomach and biles salts in the small intestine
  • Exert a beneficial effect