Mechanisms of Antibiotic Resistance Flashcards
Which of these are identified causes of the development of antibiotic resistance?
a. overprescribing antibiotics
b. poor infection control in hospitals
c. lack of hygiene and poor sanitation
d. patients not finishing their treatment
e. over-use of antibiotics in farming
f. overproduction of new antibiotics
a. overprescribing antibiotics
b. poor infection control in hospitals
c. lack of hygiene and poor sanitation
d. patients not finishing their treatment
e. over-use of antibiotics in farming
*lack of new antibiotics being developed is also an important cause!
T/F: bacteriostatic drugs can non-specifically increase the probabilities of many kinds of resistance-causing mutations
TRUE
what are 4 bacterial genetic mechanisms of antibiotic resistance?
- transformation: DNA with genes for drug resistance taken up from environment
- transduction: resistance genes transferred from one bacterium to another via bacteriophage
- conjugation: resistance genes contained in plasmid and transferred from one cell to another via pilus
- transposition: resistance genes move between plasmid and chromosomal DNA
which of these are biochemical mechanisms of antibiotic resistance?
1. decreased drug accumulation inside the bacteria (via decreased influx or decreased efflux)
2. inactivation of the drug by bacterial enzymes
3. reduction in receptor affinity for the drug
4. decreased enzymatic activation of a drug by bacteria
5. increased concentration of a metabolite that antagonizes drug action
6. decreased activity of an enzyme required to express the drug effect
7. overexpression of the target enzyme or receptor
all of these are mechanisms !
gram-negative bacteria may develop antibiotic resistance by decreasing drug influx into the cell, via mutations in ____ proteins
porin proteins
many types of bacteria have developed resistance to penicillins and cephalosporins by enzymatically cleaving the drugs with the enzyme _____
beta-lactamases (cleave beta-lactam antibiotics)
what is the mechanism of enterococcal resistance to vancomycin?
vancomycin binds D-Ala-D-Ala moiety of proteoglycans (PGs) in cell wall and interferes with cross-linking
in resistant enterococci, VanHAX operon produces enzyme that generates D-Ala-D-lactate PG that cannot be bound by drug
some anaerobic bacteria have developed resistance to ______ via decreased activation by pyruvate-ferredoxin oxidoreductase (PFOR), since this drug requires activation by the bacterial enzyme
metronidazole
the METRO[nidazole] was preceded by the FERRY[edoxin]
aminoglycoside antibiotics target bacterial ribosomes to inhibit protein synthesis
how do bacteria develop resistance to these drugs?
inactivate the drug via enzymatic modification - acetylation, phosphorylation, adenylation —> drug can’t work
(can also confer resistance via mutation in the ribosomal protein target)
how do bacteria classically develop resistance to sulfonamides (inhibit DNA synthesis)?
increase concentration of a metabolite (p-amiobenzoic acid, PABA) that antagonizes drug action
*drug is antimetabolite, so increased production of normal metabolite competes with drug
explain how bacterial mutants deficient in autolytic enzymes cannot be killed by drugs such as penicillins that inhibit cell wall synthesis?
autolytic enzymes breakdown sections of the proteoglycan (PG) matrix during bacterial growth
in absence of these enzymes, drugs that inhibit cell wall synthesis are bacteriostatic rather than bactericidal
*resistance via alteration of an enzymatic process that is unaffected by the drug but required for the drug’s cytotoxic effect
bacterial resistance to ______ classically occurs via overexpression of the target bacterial enzyme dihydrofolate redactase (DHFR), which is important in the pathway of DNA synthesis
trimethoprim
via resistance plasmids containing multiple copies of the gene encoding the target or that confer inducible expression of the gene, or mutation in a regulatory gene (repressor) that controls expression
resistant bacteria won’t DI[hydrofolate] if you TRI[methoprim]
why must you be careful about administering sub-inhibitory doses of antibiotics?
promotes selection of resistant subpopulations
how can administration of a combination of drugs prevent drug resistance in bacteria?
use drugs with different mechanisms of action and different biochemical pathways of resistance, because the resistance mutation frequency will be very low when both drugs are administered together
