22 Antibiotic Medications Flashcards
Bacteria have two different types of cell wall, how is this used by scientists?
Feature is used to classify bacteria into gram-positive and gram-negative
Where does gram-negative and gram-positive come from?
Reaction different bacteria cell walls have to a gram stain:
- Old imaging technique used to label and identify bacteria strains
- Because of structure of cell membrane
- Gram-negative - appear pink after washing the stain off
- have thin cell wall with few layers of peptidoglycan surrounded by second lipid membrane containing lipopolysaccharides and lipoproteins
- Gram-Positive - appear dark purple after staining
- thick cell wall with many layers of peptidoglycan
What is the difference between the celll-walls in Gram-positive and Gram-negative bacteria?
- Gram-positive bacteria:
- Possess a thick cell wall with many layers of peptidoglycan (polysaccharide chain)
- Gram-stain binds to the peptidoglycan layer
- Gram-negative bacteria
- Relatively thin cell wall with few layers of peptidoglycan surrounded by a second lipid membrane containing lipopolysaccharides
- less peptidoglycan + extra lipid membrane = absorbs less stain
Peptidoglycan structure consists of ______ strands made of alternating ___________ and ____________ residues cross-linked by peptides
Peptidoglycan structure consists of glycan strands made of alternating N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) residues cross-linked by peptides
What part of the bacteria cell membrane has the greatest contribution to the overall structure and shape of the bacterium?
Peptide cross-linkers between glycan strands
Individual strands of glycan are polymerized by the enzyme ________ into the peptidoglycan chain
Individual strands of glycan are polymerized by the enzyme glycosyltransferase (GT) into the peptidoglycan chain
What enzyme is responsible for generating the peptide cross-links that provide the structure to the bacteria cell membrane?
Transpeptidase (TP)
- target of many antibiotics (aka penicillin-binding protein)
What are four terms used to describe the efficacy and potency of antibiotics?
- Spectrum of activity
- Bacterial sensitivity
- Therapeutic index
- Ability to penetrate
What is Spectrum of activity?
Spectrum of activity can be narrow or broad depending on the number of different bacterial species against which they exhibit useful activity
What is bacterial sensitivity?
Sensitivity measured by assessing the ability of the bacterial strain to replicate following antibiotic exposure
- Bacteriocidal antibiotic leads to permanent loss of replicative ability
- Bacteriostatic antibiotic leads to temporary loss of growth and replication that returns following the removal of antibiotics
________\_ antibiotic leads to permanent loss of replicative ability
Bacteriocidal antibiotic leads to permanent loss of replicative ability
_________\_ antibiotic leads to temporary loss of growth and replication that returns following the removal of antibiotics
Bacteriostatic antibiotic leads to temporary loss of growth and replication that returns following the removal of antibiotics
What is the difference between broad spectrum and narrow spectrum antibiotics?
Broad-spectrum: Kills off/targets a variety of bacterial species
Narrow-spectrum: targets 1-a few species of bacteria
What is therapeutic index?
Ratio of minimum concentration likely to produce an adverse effect to the minimum concentration needed to produce a desired effect
- Wide Therapeutic index = safer
What is Ability to penetrate?
Ability of drug to get to target;
Delivery of antibiotic to site of infection is most difficult challenge of antibiotic delivery
What are four classes of antibiotics?
- Cell wall inhibitors
- Folic acid
- DNA synthesis inhibitors
- Protein synthesis inhibitors
How do antibiotics not target “self” (eukaryotic cells)
Antibiotics are designed to target pathways that are unique to bacteria (ie not found in eukaryotic cells)
What was the first cell-wall inhibitor developed?
Penicillin
-discovered by alexander fleming in 1928 - produced by fungus penicillium notatum
What antibiotic was derived from the fungus Acremonium in 1945 (similar to penicillin in that it is a cell-wall inhibitor)
Cephalosporins
Penicillins and cephalosporins are called ________ because they have an unusual 4-member ring
Penicillins and cephalosporins are called beta-lactams because they have an unusual 4-member ring
How do Penicillins and cephalosporins work?
- Inhibit cell wall synthesis by inhibiting an enzyme (DD-transpeptidase (aka penicillin-binding protein)) responsible for cross-linking components of the cell wall (bacteriocidal)
Are penicillins and cephalosporins bacteriocidal or bacteriostatic?
Bacteriocidal - permanent destruction of the bacteria (interfering with outer structure of cell kills bacteria)
Do penicillins and cephalosporins target gram-negative or gram-positive bacteria?
Originally were only effective against gram-positive but successive generations of cephalosporins have increased activity against gram-negative (although still more effective against gram-positive bacteria)
- Why?
- because gram-positive bacteria have an exposed outer peptidoglycan layer = easily accessible
What are beta-lactamases?
Bacterial enzymes (penicillinases, cephalosporinases) made by most staphylococci and many gram-negative organisms that hydrolyze the beta-lactam ring of certain penicillins and cephalosporins; confer resistance
- defense mechanism
- ARMS RACE
What are beta-lactamase inhibitors? Provide an example.
Potent inhibitors of beta-lactamases used in combinations to protect hydrolyzable penicillins (antibiotics) from inactivation
eg: Clavulanic acid
What drug named in lecture is NOT a beta-lactam but, like beta-lactams, inhibits the peptidoglycan cross-linking?
Vancomycin is not a beta-lactam but inhibits peptidoglycan cross-linking
________ is produced in nature by actinobacteria species, Amycolatopsis orientalis, commonly found in soil
Vancomycin is produced in nature by actinobacteria species, Amycolatopsis orientalis, commonly found in soil
Make a flowchart of three bacterial cell wall inhibitors:
1 2 3
Narrow and/or broad
Species
- Penicillins
- Narrow spectrum
- Penicillinase susceptible
- Penicillinase Resistant
- Narrow spectrum
- Cephalosporins
- Narrow Spectrum
- 1st generation
- Wider spectrum
- 2nd, 3rd, 4th generations
- Narrow Spectrum
- Miscellaneous
- Carbapenems
- Aztreonam
- Vancomycin
Why do bacteria need folic acid?
Bacteria use folic acid to synthesize nucleic acids that make up their DNA
(pathway unique to bacteria)
What is the synthesis pathway that bacteria use to make DNA?
- p-Aminobenzoic acid (PABA) - precursor for folate
- converted to Dihydrofolic acid using Dihydropteroate synthase
- Converted to Tetrahydrofolic acid by Dihydrofolate reductase
- Purines
- DNA
What is Para-aminobenzoic acid (PABA)?
Nutrient obtained from the environment that is the precursor for folate in bacteria
- converted into dihydrofolic acid and then to tetrahydrofolic acid by dihydropteroate synthase and dihydrofolate reductase respectively
Eukaryotes don’t have PABA and must get folic acid from _____
Eukaryotes don’t have PABA and must get folic acid from diet
What do folic acid inhibitors target?
The folate synthesis pathway in bacteria
______ and _______ resemble PABA and dihydrofolic acid respectively and interfere with PABA metabolic pathways
Sulfonamides and trimethoprim (folic acid inhibitors) resemble PABA and dihydrofolic acid respectively and interfere with PABA metabolic pathways
Which folic acid inhibitors compete with PABA
Sulfonamides compete with PABA
Which folic acid inhibitors compete with Dihydrofolic acid?
Trimethoprim competes with dihydrofolic acid for the enzyme: Dihydrofolate reductase
Which two folic acid inhibitors are usually given together and why?
Sulfonamides and trimethoprim because they block different steps in the synthesis pathway
Bacteria make protein from ______ within the bacterial _________ complex. This is unique to bacteria (eukaryotes use 80s ribosomal complex) and so allows targeting by ____________
Bacteria make protein from mRNA within the bacterial 70s ribosomal complex. This is unique to bacteria (eukaryotes use 80s ribosomal complex) and so allows targeting by Protein Synthesis inhibitors
______\_ transfers an amino acid to the growing amino acid chain (transpeptidation)
tRNA (t6) transfers an amino acid to the growing amino acid chain (transpeptidation)
What is the name of the process in which amino acids are added to a growing amino acid chain?
Transpeptidation
__________ and _________ bind to the 50s subunit and block transpeptidation
Chloramphenicol and Macrolides bind to the 50s subunit and block transpeptidation
Chloramphenicol and Macrolides bind to the and block transpeptidation
Chloramphenicol and Macrolides bind to the 50s subunit and block transpeptidation
________ bind to the 30s subunit and prevent binding of incoming tRNA
tetracyclines bind to the 30s subunit and prevent binding of incoming tRNA
tetracyclines bind to the and prevent binding of incoming tRNA
tetracyclines bind to the 30s subunit and prevent binding of incoming tRNA
How do the effects of Chloramphenicol, Macrolides and Tetracyclines differ?
Chloramphenicol and Macrolides bind to the 50s subunit and block transpeptidation
Tetracyclines bind to the 30s subunit and prevent binding of incoming tRNA
image:
C-triangle = chloramphenicol
M-triangle = Macrolides
T-triangle = tetracycline
Like tetracyclines, ________ bind to the 30s ribosomal subunit
Like tetracyclines, aminoglycosides bind to the 30s ribosomal subunit
What are three effects of aminoglycosides (where do they bind)?
Aminoglycosides bind the 30s ribosomal subunit and:
- Block the initiation of the complex
- prevent two subunits from coming together
- Cause misreading of the code on the mRNA template
- wrong aa is added (missense) (or no aa at all - nonsense)
- inhibit translocation
- process of releasing protein from ribosome
Why dont antibiotics inhibit protein synthesis in human cells as well?
- Selectivity is provided by differences in protein synthesis enzymes between humans and microorganisms and the rapid growth of bacteria
- eg: chloramphenicol doesn’t bind to the 80s ribosomal rna of mammalian cells, only the 70s ribosomal rna of bacteria
- eg mammalian cells cannot synthesize folic acid from PABA
What is bacterial resistance?
The ability of the microbe to resist the effects of antibiotics
- arms race between antibiotics and bacteria
- Consequence of evolution via natural selection
- constant division = increased opportunity for mutation = some mutations may confer a survival advantage against antibioties = survive and divide
What are four ways in which bacteria are known to develop bacterial resistance?
- Drug inactivation or modification
- Alteration of binding site
- Alteration of metabolic pathways
- Reduced drug accumulation
“Beta lactamases are enzymes produced by bacteria that inactivate antibiotics”
What type of bacterial resistance is this?
Drug inactivation or modification
Provide an example of “Alteration of binding site” which leads to bacterial resistance
Alteration of penicillin-binding proteins (aka DD-transpeptidase) in methicillin-resistant staphylococcus (MRSA)
Provide an example of “Alteration of metabolic pathways” leading to bacterial resistance
Sulfonamide resistant bacteria begin to use pre-formed folic acid from the environment rather than making it from PABA
Provide an example of reduced drug accumulation leading to bacterial resistance?
Develop efflux pumps to actively remove antibiotic from bacterial cell
(similar to p-glycoprotein pumps in the brain that pump drug out of brain)
Why might antibiotic use led to gastrointestinal distress?
Because, particularly for broad spectrum, they can target the normal gut flora thus interfering with bacterial environment of the body
- probiotic products can be used in conjunction to help limit/alleviate this
What affects might antibiotics have on the skin?
Adverse skin reactions ranging from mild rash to photosensitivity.
- use photoprotection (sunscreen) to help prevent UV damage
- Stevens-johnson syndrome
- Toxic epidermal necrolysis
What are Stevens-johnson syndrome and toxic epidermal necrolysis?
rare conditions in which the skin becomes detaches from the underlying tissue and sloughs off the body
