Antibiotics Flashcards
Antimicrobial
Interferes with growth and reproduction of a microbe
Bactericidal
Kills bacteria
Bacteriostatic
Halts bacterial growth, but does not kill bacteria
What is the most essential component to efficacy of an antibiotic?
Selective toxicity (bacteria harmed but not the host)
The bacteria structure targeted must be..
Not present in host
Different to that in the host
Or with differential access in host and bacterium
The four main antibiotic targets are…
Cell wall, nucleic acids, ribosomes and cell membranes
Wide spectrum vs narrow spectrum antibiotics
Wide spectrum - target many different bacterial types
Narrow spectrum target one individual type
What two types inhibit cell wall synthesis?
Beta-lactams
Glycopeptides
Beta lactam examples
Penicillin, amoxicillin
Beta lactam function
Block peptide cross-linking in growing cell wall, prevent PG synthesis
Target of beta-lactams (penicillin)
Target penicillin binding proteins, which are required for proteoglycan synthesis
Transpeptidase are penicillin binding proteins which are targets of Beta lactam antibiotics.
Similar in structure to D-alanyl-D-alanine peptide of proteoglycan cross link, so binds in active site for transpeptidase enzyme - preventing final cross-linking step.
Beta lactam resistance
Resistance results from bacteria using D-lactate instead of alanine in PG
Is beta lactam bactericidal or bacteriostatic?
Bactericidal but kills cells only when they are growing. For example, no growth, no cross linking needs to occur.
Glycopeptide example
Vancomycin
Role of glycopeptide antibiotics
Large hydrophilic molecule, forms hydrogen bonds with terminal D-alanyl-D-alanine, peptide of proteoglycan cross links.
Targets PG itself so only active on gram positive bacteria.
Is glycopeptide bactericidal or bacteriostatic?
Bacteriostatic
3 bacterial protein synthesis (ribosome) inhibiting antibiotics (and examples)
Macrolides (erythromycin)
Aminoglycosides (gentamicin, tetracycline, streptomycin)
Chloramphenicol
Macrolide action
Inhibit transcription by binding to 50s subunit and prevent escape of tRNA once it has donated its amino acid. Thus, new tRNA cannot attach.
Bacteriostatic
Aminoglycoside action
Inhibition of the initiation complex and of messenger RNA.
No translation and no protein production
Bacteriostatic
Chloramphenicol action
Inhibits peptidyl transferase, preventing synthesis of new peptide bonds, selectively bacteria as binds to 50s subunit not human 60s.
Bacteriostatic
Why are ribosomes an appropriate antibiotic target?
Ribosomes are a key target as very different sizes in eukaryotes and prokaryotes.
Bacteria (30s and 50s unit), humans (60s and 40s unit).
Inhibitor of transcription antibiotic example
Rifamycin (rifampicin)
Rifamycin action
Inhibitors of (m)RNA synthesis, by affecting bacterial RNA polymerase without affecting RNA pol of human cells.
Anti-tuberculosis
Bactericidal
What antibiotic inhibits folate metabolism (and DNA synthesis?
2,4-diaminopyridines (i.e trimethoprim)
What antibiotics inhibit DNA synthesis by binding DNA gyrase?
Quinolones, fluoroquinolones (i.e ciprofloxacin)
Inhibits DNA gyrase (topoisomerase in prokaryotes)
UTIs, lower respiratory tract infections
Bactericidal
What is DNA gyrase?
Prokaryote topoisomerase (DNA uncoiler)
Role of sulphonamides
Antifolates, block the synthesis of tetrahydrofolic acid, which is required in the synthesis of nucleic acids.
Sulphonamide compete with PABA in active site of dihydropteroate synthetase (important enzyme in synthesis of THFA).
When would one combine antibiotics?
Empiric therapy with broad spectrum antibiotics is important when the agent is unknown.
Can give complimentary, synergistic action to stamp out an infection
Combination of bactericidal and bacteriostatic is important for killing a population
Likely to reduce emergence of resistance as a wider range of bacteria can be killed
When and why would one use specific therapy?
Transition to a specific therapy when identification has been done - reduces resistance risk (less bacteria species are put under a selection pressure).
What is the MIC, why is it important?
Minimum inhibitory concentration, antibiotic must remain above this at all times
Target site insensitivity resistance
Changes to ribosome structure in erythromycin resistance.
Erythromycin can no longer bind and inactivate the ribosome
Enzymatic inactivation resistance
Beta-lactamases in penicillin resistance: Beta-lactamases are enzymes produced by bacteria that provide multi- resistance to β-lactam antibiotics such as penicillin.
Beta-lactamase provides antibiotic resistance by breaking the antibiotics’ β-lactam ring open, deactivating the molecule’s antibacterial properties.
Beta lactamase inhibitors provide a therapeutic option to combat resistance.
Cell wall impermeability resistance
Mutant porins in G-bacteria
Drug export resistance
Gyrase mutations in quinolone resistance
Increased efflux resistance
Through the presence of tetracycline membrane pumps
Target modification resistance
Quinolones, penicillins, change of receptor
Target amplification resistance
Sulphonamides, where causes many copies of enzyme to be produced, leading to competitive inhibition.
MRSA resistance
MRSA - Mec genetic element encodes a different PBP i.e. altered target site
Therefore, active site does not bind methicillin or other beta-lactam antibiotics.
Therefore, the PBP can continue to catalyse the transpeptidation reaction required for peptidoglycan cross-linking, enabling cell wall synthesis in the presence of antibiotics.
Integrons
Genetic mechanisms that allow bacteria to adapt and evolve rapidly through the acquisition, stockpiling and differential expression of new genes
Genes are embedded in a gene cassette, which carries one promoterless ORF together with a recombination site
Plasmids
Transferrable between strains
Many copies
Move by transformation or conjugation
Biofilms
Collective of one or more types of microorganisms that can grow on many different surfaces.
Infections associated with the biofilm growth usually are challenging to eradicate.
This is mostly due to the fact that mature biofilms display antimicrobial tolerance, and immune response evasions.
Contains a supportive glycocalyx where bacteria can grow resistant to antibiotic drug.
Overuse of antibiotics
Antimicrobial resistance is mainly caused by the overuse of antimicrobials.
This leads to microbes either developing a defence against drugs used to treat them, or certain strains of microbes that have a natural resistance to antimicrobials becoming much more prevalent than the ones that are easily defeated with medication
Which of the following antibiotics acts by inhibiting bacterial transcription?
Rifampicin
Which of the following antibiotics is an example of the macrolide class of antibiotics that inhibits bacterial protein synthesis by binding to the bacterial ribosome?
Erythromycin
Which of the following antibiotics inhibits the bacterial enzyme DNA gyrase, leading to disruption of bacterial
DNA synthesis?
Ciprofloxacin
What class of antibiotic is penicillin?
A beta lactam
What is the bacterial enzyme inhibited by penicillin?
Transpeptidase
Antibiotic that inhibits protein synthesis by blocking binding of tRNA to 30S
Tetracycline
