Lecture 6/7: Growth Control and Molecular Biology Flashcards
What are the mechanisms of drug resistance?
- Impermeability - drug can’t get into cell
- Efflux - infected cell ejects drug from cell w/ enzyme
- Inactivation - enzyme degrades drug
- Mutation in target - drug target mutates
- Absence of target
- Alternative Biochem pathway - cell uses different pathway to get around target of drug
What are the origins of the evolution of drug resistance?
Drugs are produce by microorganisms b/c the microorganisms must be able to resist their own antibiotics There is no universal antibiotic Antibiotics also function as signaling molecules
How has antibiotic resistance spread?
Overuse
- 20 percent of patients need antibiotic treatment
- 80 percent of patients receive antibiotic treatment
How is gonorrhea a case study of antibiotic resistance?
Penicillin used from 1940-1990
Ciprofloxacin used in early 1990s
Ceftriaxone used in late 1990s
Antibiotics only effective as long as we have a continuous supply of new types of antibiotics
How is antibiotic resistance spread through non-medical overuse?
50-70 percent of antibiotics used for livestock/agriculture
We select for antibiotic-resistant bacteria by creating these antibiotic rich habitats
What is an ‘‘invincible’’ pathogen? What is an example?
Resistance to all known microbial agents
MRSA -Methicillin-Resistant Staphylococcus aureus
How do we reverse antibiotic resistance?
decrease usage = decrease selection = decrease prevalence of resistance
-large scale coordinated effort
How do we deal with antibiotic resistance? What is the economic paradox of antibiotics that makes dealing with it less likely?
We can discover and develop new antibiotics
Economic paradox is
- low return on investment b/c not a lifelong medicine
- loss of value over time b/c resistance of development
How do we discover new drugs?
- New analogs of existing compounds
- Computer drug design
- Natural products
- Drug combinations
- Bacteriophage therapy
How do we use new analogs of existing compounds to search for new antimicrobial drugs?
Semisynthetic approach
-changing functional groups on existing compounds
How do we use computer drug design to search for new antimicrobial drugs?
Computer based design of new molecule to mimic/outcompete normal substrate of disease enzyme
- competitive inhibition
- must know very detailed information about disease like shape/structure
How do we use natural products to search for new antimicrobial drugs?
Most antibiotics found in soil
- actinomycetes found in soil and important for antibiotic production
- more difficult but can find antibiotics in marine sediment
How do we use drug combinations to search for new antimicrobial drugs?
Using an antibiotic+compound inhibiting resistance
- finding something that inhibits the mechanism for antibiotic resistance and combining it with an antibiotic
- eg. efflux pump inhibitor + antibiotic
How do we use bacteriophage therapy to search for new antimicrobial drugs?
We use viruses to destroy specific pathogens
What are the functions of the different genetic elements?
Replication - DNA to DNA
Transcription - DNA to RNA
Translation - RNA to protein
What is the function of DNA/RNA?
DNA - deoxyribonucleic acid
- genetic blueprint for cell
- information replication and storage
RNA - ribonucleic acid
- converts blueprint to amino acids
- information processing
What is the structure of DNA?
Double stranded
- sugar-phosphate backbone
- held together by Nitrogenous bases
Antiparallel
-5’ to 3’ and 3’ to 5’
What are the different types of grooves in the DNA double helix pictured?
Major groove and Minor grooves
How is DNA packaged into the cell? What enzyme is responsible for this?
DNA Supercoiling
-twisting DNA into coils takes up less space
Topoisomerases are responsible for this
What are the types of Topoisomerases?
Class I Topoisomerases
-Single stranded break
Class II Topoisomerases
- Double-stranded break
- eg DNA Gyrase