Antibiotics Flashcards
Antibiotics work on ____ not ______
bacteria, viruses
The ideal target for antibiotics is
- One of the essential processes of the bacterial cell
- The process differs from the human cell
When the cell wall is the target, the _____ and the _____ is targeted
peptidoglycan layer, membrane(s)
When DNA/ RNA synthesis is targeted, ____ involved in the processes are targeted
Enzymes
When the folate system is targeted, the _____ is targeted
metabolism
when protein synthesis is targeted the ______ ______ are the main target
bacterial ribosomes
The golden age of antibiotic discovery was
1940’s- 1960’s
The last new class of vaccines was in the
1980s
many drugs are active against Gram _____ but not against gram ____ because
positive, negative, gram-negative bacteria possess two membranes which makes it twice as hard for antibiotics to penetrate
Horizontal gene transfer
the transfer of genes between bacteria in the same generation
Vertical gene transfer
the transfer of genes between bacteria through reproduction (next generation)
Antibiotic resistance results from
selective pressure
Acquired resistance
bacteria acquire resistance through gene transfer
Intrinsic resistance
Built-in features that give the bacteria resistance
Drugs that target peptidoglycan are active against _____
Gram-positive bacteria
Why are gram-negative bacteria harder to target than gram-positive?
- possess 2 membranes (permeability is low)
- non charged
Mechanisms of antibiotic resistance by bacteria
- inactivation of drug by enzymes
- activation of drug efflux pumps
- Inhibition of drug uptake
- Alteration of drug target
Porins
protein channels in the membrane of bacteria
decreased expression of porins leads to
decreased uptake of antibiotics due to fewer channels to enter through
Current approaches to antibiotics
- chemically modifying existing drugs
- Combination therapies
The idea behind combination therapies is synergy which means
combo activity > individual activities
Ways to overcome efflux pumps
- inhibit EP gene expression
- Change the drug structure
- inhibit the assembly of pumps
- remove the energy source
- Blocking the pore
- application of competitive/ non-competitive inhibitor with drug
How does changing the drug structure help reduce antibiotic resistance?
The Efflux pump doesn’t recognize the drug and doesn’t pump it out of the cell
Efflux pump
On the surface of the bacteria to pump out unknown bodies.
what is the energy source of efflux pumps
proton motive source
limitations to efflux pump inhibitors
- Human cells have efflux pumps (can be affected)
- Inhibitors must get into the cytosol (difficult to get past membranes)
- Pharmacokinetics (drugs move through the body at different rates/ need right [conc] at the same time)
How do adjuvants assist vaccines?
weaken the membrane of the bacteria cell (cells pack looser)
Weak membrane perturbation leads to
- more influx of antibiotics
- efflux pump inhibition
Adjuvants lead to _____ cell uptake
increased
H+ gradient across the membrane allows
efflux pumps to work
Antimicrobial Peptides are
- based on natural molecules
- part of innate immune response
- short proteins (peptides)
- Amphiphilic
Advantages of AMP’s
- Target the lipids on the bacteria
- bacterial resistance is less likely
Disadvantages of AMP’s
- Can be hydrolyzed by enzymes
- Cost more money than small molecules
AMP’s are _____ which means they carry a ____ charge, this makes them attracted to the ______ charged bacteria
Catatonic, positive, negatively
AMP’s have ______ interactions with the membrane of bacteria
Electrostatic
AMP’s will interact with the ______ core
hydrophobic
The types of structures of AMPs include
- Alpha helical
- Beta Sheets
- disordered
How are AMP’s hidden from enzymes
- change conformation of the amino acids
- changed to peptoids
What are peptoids??
Side chains are attached to Nitrogen instead of Carbon
What are bacteriophages
viruses that only infect bacteria
Lytic phages are used to
break open cells
Bacterial virulence factors
molecules produced by bacteria that give them an advantage
Advantages to anti-virulence strategies
- decreased selective pressure
- specific to pathogens
Disadvantages to anti-virulence strategies
- Narrow spectrum (need to know bacterium causing the infection)
- Doesn’t kill the bacteria, only weakens it
Class I anti adhesives
mimic adhesions and compete for host cell binding
Class II anti adhesives
directly block and interfere with adhesion-host cell recognition
Class III anti adhesives
Inhibit the biosynthesis of surface presentation of adhesins
Class IV anti adhesives
inhibit host receptor surface presentation
Class V anti adhesives
antibodies that target adhesins, inhibiting host recognition
