Lecture 33

Front 1

Prions

Back 1

- thought to cause mad cow's disease

- infectious proteins (no DNA or RNA)

Front 2

Prion Protein (PrP)

Back 2

- exist in all human and mammalian brains

- believed to play a role in normal human function, function not known

- 2 folded forms: cellular and Prion

Front 3

Cellular PrP

Back 3

- made by cells in brain throughout life

- non-infections

Front 4

Prion PrP

Back 4

- can be acquired

- often by eating

- can act as an enzyme, refolding cellular protein to make more Prion PrP

- cells detect lack of cellular PrP, so they generate more which is eventually converted

- build up of Prion PrP forms tangles or plaques which interferes with neuronal function

- prion disease often called spongiform encephalopathies because of brain damage observed

Front 5

Creutzfeld-Jakob Disease

Back 5

- Varient: injested/acquired prion PrP converts cellular PrP to indice disease

- Spontaneous: cellular PrP converts to Prion PrP for unknown reasons (40% of humans have a variation of cellular PrP that is more susceptible to folding

Front 6

Sources of Prions

Back 6

- ingestion of nervous tissue is primary source

- other animal sources: eyes, skeletal muscle

- transplantation of nervous tissue and blood

- Acquisition of Prion PrP through tainted medical supplies

Front 7

Prion Concerns

Back 7

- Normal cooking and sterilization procedures do not deactivate prions

- incineration or special enzymes are required

- human trials of drugs to stall CJD are ongoing

Front 8

Chlamydia

Back 8

- Most frequently reported STD in the US

- Caused by obligate intracellular pathogens (Chlamydia trachomatis and pneumoniae)

- Often silent

- Can cause serious problems if untreated

- Pelvic inflammatory disease in women

- Testicular and urethral infections in men

Front 9

Gonorrhea

Back 9

- Cause by Gram-negative diplococcus (Neisseria gonorrhoeae)

- incrementally developed resistance used in treatment over decades

- most infected men exhibit symptoms

- women are usually asymptomatic

- reinfection is possible due to phase variation

Front 10

Selective Toxicity

Back 10

- key requirement of antibiotic

- drug kills microorganism without harming host

- May have side effects at high concentration

- Chloramphenicol can interfere with our ribosomes (RBC development)

- May cause allergic response

- Must affect specific physiology to microbes (peptidoglycan cell wall, ribosome, DNA/RNA Polymerase structure, biopathway unique to bacteria)

- Antibiotics should target essential function

Front 11

Penicillin

Back 11

- inhibitor of cell wall synthesis is only effective during cell wall synthesis and antibiotic must be taken until all cells leave stationary phase

Front 12

Broad-Spetrum

Back 12

- Effective Against Many Species

Front 13

Narrow-Spectrum

Back 13

- effective against few or single species

Front 14

Source of Antibiotics

Back 14

- discovered as natural products

- often modified chemically during synthesis to increase efficacy and decrease human toxicity

Front 15

Spectrum of Activity

Back 15

- range of organisms over which a drug has an effect

- most antimicrobial therapeutics affect a narrow group of related organisms with shared physiology

Front 16

Kirby-Bauer Disk Susceptibility Test

Back 16

- Test strain sensitivity to multiple antibiotics

- multiple disks with different antibiotics

- size of cleared zones reflect relative sensitivity

Front 17

Bacteriocidal

Back 17

- kills the target organism

- many only affect actively growing cells

- inhibitor of cell wall synthesis is only effective during cell wall synthesis and antibiotic must be taken until all cells leave stationary phase

Front 18

Bacteriostatic

Back 18

- only prevents growth of organism

- immune system removes infection

Front 19

Antibiotic Resistance

Back 19

- growing problem

- antibiotics overused

- overprescribes, used in farm feed

- exerts selective pressure for drug resistant strains

- many strains become multiply drug-resistant

Front 20

Destroying The Antibiotic

Back 20

- antibiotic resistance mechanisms

- many bacteria make beta-lactamase

- destroys penicillin analogues

Front 21

Modifying the Antibiotic

Back 21

- antibiotic resistance mechanisms

- enzymes modify aminoglycosides (via acetylation, phosphorylation, adenylation)

- can no longer bind the ribosome and interferes with translation

Front 22

Changes the Antibiotic Target

Back 22

- antibiotic resistance mechanisms

- modify target protein so that antibiotic no longer binds

- most common streptomycin-resistance mechanism

Front 23

Drug Efflux

Back 23

- antibiotic resistance mechanisms

- via ABC transporters

- multidrug resistance (MDR) exporter

- pumps drug out of cell

- confers resistance to several classes of antibiotics at once

Front 24

Essential Function

Back 24