Antibiotic Resistance Flashcards
How is antibiotic resistance acquired?
Mutation and horizontal gene transfer
How can resistant strains of antibiotics be selected?
By the misuse and overuse of antibiotics
What are the 3 major antibiotic resistance mechanisms?
- Prevent access to target
- Modify or protect antibiotic target
- Modification/inactivation of antibiotics
What are some examples of antibiotic tolerance mechanisms?
- Biofilm formation
- Persister cells
- Spores
What are antibiotics synthesized by?
Molds or bacteria
Prior to antibiotics and vaccines what diseases caused one third of all deaths?
- Pneumonia
- TB
- Diarrhea and enteritis
- Diptheria
When and where was penecillin first discovered?
St. Mary’s hospital in London, September 1928, by Alexander Fleming
How many antibiotics have been developed since penicillin was introduced?
over 140
How many lives do antibiotics save each year in the USA?
over 200,000
*Adding 5-10 years to US life expectancy
What are the antibiotic targets?
- Cell wall synthesis/integrity
- RNA synthesis
- Amino-acyl-tRNA synthetase
- DNA replication/repair/segregation
- Protein synthesis
- Folic Acid synthesis (tetrahydrofolate)
Which antibiotics target Cell wall synthesis?
- B-lactams
- Glycopeptides
- Bactitracin
- Fosfomycin
Which antibiotics target RNA synthesis?
Rifampin
Which antibiotics target Amino-acyl-tRNA synthesis?
Mupirocin
Which antibiotics target DNA replication?
Quinolones
Fluoroquinolones
Metronidazole
Which antibiotics target protein synthesis?
Targeting of 30s:
- Aminoglycosidese
- Tetracyclines
Targeting of 50s:
- Chloramphenicol
- Macrolides
- Lincosamides
- Streptogramins
- Everninomycin
- Oxazolinonones
Which antibiotics target Folic acid synthesis?
Sulfanomides
Trimethoprim
What is the estimated number of illnesses caused by antibiotic resistance every year?
2,049,442
What is the estimated number of deaths caused by antibiotic resistance?
23,000
If the current trend continues, antibiotic resistant bacteria are expected to cause the premature death of how many people per year globally by 2050?
10-300 million
What are the steps of how antibiotic resistance happens?
- Lots of germs, a few are drug resistant
- Antibiotics kill bacteria causing the illness, as well as good protecting the body from infection
- The drug-resistant bacteria are now allowed to grow and take over
- Some bacteria give their drug-resistance to other bacteria causing more problems
Bacterial resistance facilitated by __________, ______, and by strong selective pressures from increased use of _______ in both clinical and agricultural settings
- Large numbers of bacteria
- HGT
- Antibiotics
What does it mean for bacteria to restrict antibiotic access?
Prevent drug from getting in or pump the drug back out before it affects the target
What does it mean for bacteria to modify antibiotic target?
Target is altered structurally or target is over expressed, requiring much more drug
What does it mean for bacteria to modify the antibiotic?
Drug is inactivated before affecting target
T/F Bacteria can modify expression of bacterial factors needed to activate the antibiotic (like a prodrug)
True
*this is also a mechanism of resistance in addition to the main 3
How would an antibiotic restrict access of antibiotic to target?
Alter envelop to inhibit uptake or boost expression of efflux pumps
How would bacteria over express the target?
- Change in promoter
- Change in regulator
- Change in Gene copy number
How would bacteria Modify the target?
- Mutation of gain of modifying enzyme
- Over expression of target
What are two ways that a bacteria can inactivate the antibiotic?
- Inactivation by hydrolysis
2. Inactivation by steric hindrance
What are 3 things that can be done by Aminoglycoside-inactivating enzymes to modify aminoglycosides?
- N acetylation
- O phohphorylation
- O adenylation
*These modifications disrupt hydrogen-bonding network used to bind 16s rRNA
Flavodoxin activates Metronidazole in which bacteria?
- H. pylori
2. P. gingivalis
KatG activates Isoniazid. Which bacteria would produce KatG
Mycobacterium TB
Resistance is acquired by _______ and ______
- Mutation
2. Horizontal gene transfer
In E. Coli, resistance to Streptomycin can arise due to a spontaneous mutation that occurs at what rate?
1 in a billion
**Fast growth and high numbers make this a significant rate
List 4 multidrug resistant bacterial pathogens that are becoming increasingly common
- Extended-spectrum B-Lactamase producing Enterobacteriaceae
- Carbapenem-Resistant Enterobacteriaceae
- C. Diff
- Super Neisseria gonorrhea
What contributes to the selection and spread of multi drug resistant strains of bacteria?
- Overuse of antibiotics
- Overpopulation
- Poor hygiene
- Travel
Name a pathogen that is Priority 1 and is carbapenem resistant
- Acinetobacter baumannii
- Pseudomonas aeruginosa
Name a pathogen that is priority 1, carbapenem resistant, and ESBL producing
Enterobacteriacea
Name a pathogen that is Priority 2 and is vancomycin resistant
Enterococcus faecium
Name a pathogen that is priority 2 and is methicillin resistant, vancomycin-intermediate and resistant
S. aureus
Name a pathogen that is priority 2 and is clarithromycin resistant
H. pylori
Name a pathogen that is priority 2 and is fluoroquinolone resistant
- Campylobacter spp
- Salmonellae
Name a pathogen that is priority 2 and is fluoroquinolone and cephalosporin resistant
Neisseria gonorrhoeae
Name a pathogen that is priority 3 and is penicillin-non-susceptible
Strep pneumo
Name a priority 3 pathogen that is ampicillin resistant
H. flu
Name a priority 3 drug that is fluoroquinolone resistant
Shigella
What are 3 deterrents from the development of new antibiotics?
- Costs
- Pharmacokinetics
- Potential side effects
T/F Bacteria that are normally susceptible to antibiotics may be able to tolerate the drugs under some conditions
TRUE
Bacteria present within _____ are often protected from antibiotic treatments
biofilms
What percent of human infections may involve biofilms
over 65%
Antibiotic tolerance is important in what 4 types of pathogens?
- Within intracellular niches
- Spores
- Within biofilms
- Persister cell formation
Name 6 ways that biofilms can enhance the ability of bacteria to tolerate antibiotics
- Extracellular matrix
- Increased stress resistance
- Increased genetic exchange
- Persister cell formation
- Decreased metabolism
- Altered protein expression
What are persister cells?
Dormant bacteria that are insensitive to many stresses and antibiotic treatments
