antibiotic resistance Flashcards
1
Q
types of bacteria
A
- gram positive: cell wall has a thick peptidoglycan layer which is relatively porous, allowing substances to pass through it quite easily -> greater access to antibiotics, allowing them to more easily penetrate the cell and/or interact with the peptidoglycan itself
- gram negative: peptidoglycan layer is greatly reduced and is further protected by a second, outer membrane -> more effective at preventing large molecules e.g. antibiotics from entering the cell
2
Q
types of antibiotic
A
- broad spectrum: generally effective against both gram -ve and +ve
- narrow spectrum: generally effective against either gram -ve or +ve
- bactericidal: kill the bacteria
- bacteriostatic: inhibit bacterial growth/processes
3
Q
cell wall synthesis inhibitor antibiotics
A
- main way bactericidal antibiotics work
- block the production ofpeptidoglycan
- cross-linking between peptidoglycan chains forms a strong, mesh-like structure that gives the cell wall structure and rigidity and protects the underlying cell membrane from osmotic damage -> disruption can result in cell lysis
- does not affect the host cell as human cells do not have cell walls
- examples: beta-lactams (penicillins and cephalosporins)
4
Q
protein synthesis inhibitor antibiotics
A
-ribosomes are made up of one large and one small subunit which differ structurally and chemically between prokaryotic and eukaryotic ribosomes
-this provides antibiotic targets in the bacterial pathogen which are not present in the host cells, minimising the side effects for the human
Example: streptomycin
5
Q
nucleic acid synthesis inhibitor antibiotics
A
- some antibiotics inhibit bacterial enzymes that unwind the DNA double helix -> replicationis blocked -> cell division cannot occur
- some antibiotics inhibit mRNA synthesis by binding to and inhibiting RNA polymerase -> stops new proteins being made
6
Q
metabolic reaction inhibitor antibiotics
A
- antibiotics that disrupt essential bacterial metabolic pathways act asantimetabolites and have a similar shape to naturalmetabolites(so can bind to the enzyme’s active site) but are different enough to interfere with normal cell function
- some antibiotics (e.g. trimethoprim) inhibit folic acid synthesis, a vitamin which bacteria, unlike humans, must make themselves as it cannot be transported into the bacterial cell by diffusion/active transport
- bacteria use folic acid to synthesize the nucleic acids that make up their DNA
- the antibiotic out-competes dihydrofolic acid to react with a specific bacterial enzyme in the pathway (by competitive inhibition) thereby interrupting folic acid synthesis and inhibiting bacterial growth
7
Q
modifying the target
A
- changes to the structure of the target that prevent efficient antibiotic binding but still enable the target to carry out its normal function will confer antibiotic resistance
- changes to the structure of antibiotic targets can be caused by genetic mutations or by adding chemical groups
8
Q
Destroying/modifying antibiotic molecule
A
- β-lactamases: deactivate the β-lactam ring of β-lactam antibiotics, preventing them from binding to their target
- Extended-spectrum beta-lactamases (ESBL) areenzymes that confer resistance to mostbeta-lactam antibiotics
- β-lactamases can deactivate almost all of the β-lactam antibiotics currently in therapeutic use -> their presence significantly reduces the available treatment options for infections
- one successful strategy for treating these infections is to combine antibiotic treatment with a β-lactamase inhibitor (clavulanic acid)
- antibiotic-modifying enzymes modify the antibiotic’s structure by adding chemical groups to prevent it from binding to its target e.g. against streptomycin
9
Q
Preventing entry, increasing exit
A
- for antibiotics to enter gram -ve bacteria, they diffuse across non-specific, channel-forming proteins called porins which are embedded in the outer membrane
- some bacteria can remove antibiotics by efflux pumps (transport proteins in the bacterial membrane which actively transport antibiotics out of the cell)
- some efflux pumps are specific (can only transport some antibiotics out of the cell) but some are multi-drug resistant (can transport many antibiotics out of the cell)
10
Q
Co-trimoxazole Resistance
A
- co-trimoxazole is a mixture of trimethoprim and sulfamethoxazole
- bypass strategy: overproduction of dihydrofolate reductase (the enzyme which co-trimoxazole binds to) through mutations in the promoter region of the DNA encoding these enzymes
- these mutations result in the production of increased quantities of the enzyme, “overwhelming” the ability of co-trimoxazole to inhibit folate production and permitting bacterial survival
11
Q
Intrinsic vs Acquired Resistance
A
- intrinsic: innate ability of bacteria to resist the action of an antibiotic because of its structural or functional characteristics
- may occur because bacteria lack the target for a particular antibiotic or because the drug can’t get to its target
- gram -ve bacteria are often intrinsically resistant because of its outer membrane which is impermeable to many antibiotics
- Acquired: bacterium acquires the ability to resist particular antibiotics
- only found in some populations of a bacterial type, making acquired resistance harder to track
12
Q
Horizontal gene transfer methods
A
- Conjugation: plasmids are transferred between two contacting bacteria via a hollow tube (pilus)
- Transformation: bacteria take up DNA from their environment across the cell wall which can then be incorporated into their genome
- Transduction: bacteriophages (viruses that infect bacteria) insert their DNA into the bacterial cell genome. When it is time for the virus to replicate, it cuts out its DNA from the bacterial genome, but this may be imperfect and some bacterial DNA is accidentally cut out too. When the virus infects a different bacterial species, they carry this bacterial DNA, which may contain AR genes, and insert it into the genome of the new host bacterium
13
Q
Misuse of antibiotics
A
- not completing the course -> failure to maintain the antibiotic at a high enough level to kill all the bacteria -> opportunity for resistant bacteria to be selected and resistance to develop
- patient may start to feel better after a few days and stop taking antibiotic, but the surviving resistant bacteria will soon multiply, symptoms will return and the antibiotic will no longer be effective at the original dose used
- empiric treatment -antibiotic therapy administered without a definitive diagnosis and based on clinical observation and experience, may select for multi-drug-resistant bacteria and encourage the spread of resistance due to wrong doses being administered
14
Q
Discovery Void
A
- the last class of antibiotic approved for clinical treatment (lipopeptides), was in 1987
- it can take 12-15 years to develop a new drug and to clear regulatory hurdles, at a very high cost
- treatments are taken only for short periods of time (unlike medicines for chronic diseases) and they become less effective as resistance develops, meaning that the supply of new drugs constantly needs to be replenished
15
Q
Natural Antibiotics
A
- complex chemicals which are synthesised stepwise by the bacteria or fungi that produce them in a series of enzyme-catalysed reactions
- they are secondary metabolites produced in the stationary phase of growth
- in manufacturing, pure cultures of antibiotic-producing bacteria and fungi are grown in huge bioreactors containing thousands of litres (batch fermentation)
- favours antibiotic production by limiting the time that cells spend in the exponential growth phase
- the antibiotic products are then harvested and purified to make them safe for human use
