Exam 4 Lecture 21

• What part of the LPS of gram negative bacteria acts as an endotoxin?

  Lipid A
• List Lipid A features

  Heat stable, toxic in nanogram amounts, but weakly immunogenic
• What does bacterial LPS do during infection?

  Binds TLR4, activates NFkB to transcribe genes for cytokines
• The cytokines that are produced result in what when they are in uncontrolled amounts:

  Fever, inflammation and blood vessel leakage, causing hypotension
• Lowered blood pressure

  Hypotension
• Blood vessel leakage -> hypotension leads to what

  Septic shock
• Endotoxin stimulates cytokine release via what

  TLR4
• Cytokine release steps via endotoxin

  1. LPS is released from gram - bacteria

  2. LPS binds to TLR4

  3. Signaling cascade is activated, including NF-kB

  4. NFkB leads to transcription of genes in the nucleus of the host cell

  5. Transcription produces cytokines which are released from the host cell
• In terms of microbial control, what does -cidal mean?

  To kill
• In terms of microbial control, what does static mean?

  Inhibits growth
• Process by which all living cells, spores and viruses are destroyed or removed

  Sterilization
• Reduction of microbial population, destruction of pathogens

  Disinfection
• Reduction of microbial contamination to levels safe by public health standards

  Sanitization
• Chemical agent applied to tissue to prevent infection by inhibition or killing

  Antiseptic
• Mechanical removal of microbes

  Filtration
• Chemical agents used in microbial control

  Gases
• Physical agents used in microbial control

  Radiation and heat
• What are two forms of radiation used in microbial control

  UV and ionizing (x and gamma rays)
• Type of radiation that can sterilize, but poorly penetrates (is mostly used to disinfect)

  UV
• Type of radiation that penetrates and sterilizes

  Ionizing (x and gamma rays)
• What type of heat is more effective: moist or dry

  Moist
• What machine uses steam under pressure to sterilize?

  Autoclave
• What are the autoclave settings?

  15 lbs/sq in

  121 degrees C

  15 minutes
• Doesn't sterilize but kills most pathogens including Listeria, Salmonella, and Campylobacter

  Pasteurization
• Beer and fruit juice pasteurization protocol

  63 degrees C

  30 minutes

  Rapid cool
• Milk pasteurization protocol

  72 degrees C

  15 seconds

  Rapid cool
• Antimicrobial agents are:

  Used to treat disease

  Destroy pathogenic microbes or inhibit growth

  Most are antibiotics
• Microbial products that kill or inhibit

  Antibiotics
• Streptomyces requires how many enzymatic reactions to make tetracycline?

  70
• Paul Ehrlich discovered what?

  Selective toxicity
• Alexander Fleming accidently rediscovered what?

  Penicillin
• Florey, Chain, and Heatley did what with penicillin?

  Purified it and injected it into mice infected with Staphylococcus

  The mice survived
• Selman Waksman did what

  Cultured over 10,000 strains of soil bacteria and identified streptomycin
• What kind of antibacterial drugs attack many different pathogens?

  Broad-spectrum
• What kind of antibacterial drugs attack only a few different pathogens?

  Narrow-spectrum
• Considerations for developing a clinically-useful antibiotic

  - $300 million, 15-20 years (20 and 2 rule = takes 20 years to make and in about 2 years you will start to see antibiotic resistance)

  - Allergenic? toxic?

  - Broad vs narrow

  - Reach effective concentration

  - Not inactivated

  - Doesn't eliminate microflora (Pseudomonas colitis)
• What is Pseudomonas colitis

  Disruption in microflora

  Caused by Clostridium difficile (C diff)

  Anaerobic, spore-forming, toxin-producing bacillus
• What do antimicrobial agents target?

  Cell wall, plasma membrane, nucleic acid synthesis, protein synthesis, and metabolic enzymes
• What antibiotics are cell wall synthesis inhibitors?

  Penicillins (B-lactams)

  Cephalosporins (B-lactams)

  Vancomycin

  Bacitracin
• List penicillin features

  Most are narrow spectrum (Gram +) and cidal

  Ampicillin and Amoxicillin are broad Gram + and - examples

  Made of B-lactam ring and R group