Antibiotics

Question 1

antibiotics

Answer 1

soluble compounds that are produced and released by microorganisms and inhibit the growth/kill other microorganisms
→ expanded to include synthetic compounds

Question 2

bacteria

Answer 2

single celled organisms
present in most habitats
symbiotic and parasitic relationships with plants and animals

1. aerobic or anaerobic
2. shape
3. cell wall

Question 3

bacterial shape

Answer 3

bacillus (rod)
coccus (sphere)
spiral
other shapes

strepto - chain
diplo - pair
staphylo - cluster

Question 4

cell wall

Answer 4

made up of peptidoglycan - polysaccharide chains
glycan strands with alternating N-acetylglucosamine and N-acetylmuramic acid residues cross-linked by peptides

Question 5

gram-positive

Answer 5

bacteria with thick cell wall with many layers of peptidoglycan
take up gram stain → pink dye

Question 6

gram-negative

Answer 6

bacteria with thin cell wall
a few layers of peptidoglycan surrounded by a second lipid membrane with lipopolysaccharides and lipoproteins

most bacteria

Question 7

glycosyltransferase

Answer 7

enzyme that polymerizes individual glycan strands into peptidoglycan chain

Question 8

transpeptidase

Answer 8

enzyme that cross links the glycan strands (creates peptide link)

targeted by many antibiotics

Question 9

normal flora

Answer 9

microbial species that cover us
we rely on normal flora to promote our health and own physiological function

only cause problems if immune system is weakened or if they access a normally sterile part of body (ex. bowel perforation)

Question 10

pathogenic bacteria

Answer 10

pathogens do not require the host to be immunocompromised or injured
developed specialized mechanisms for crossing cellular and biochemical barriers; elicit specific responses from hosts → survival + multiplication of pathogen
ex. coughing/sneezing → spread of bacteria to another host

Question 11

diseases caused by pathogenic bacteria

Answer 11

food borne illnesses
STDs
skin infections
highly infectious diseases

Question 12

antibiotic efficacy

Answer 12

1. spectrum of activity
2. bacterial sensitivity
3. therapeutic index
4. ability to penetrate

Question 13

spectrum of activity

Answer 13

narrow or broad spectrum → number of bacterial species against which they exhibit useful activity

Question 14

bacterial sensitivity

Answer 14

measured by assessing ability of strain to replicate following antibiotic exposure

Question 15

bacteriocidal

Answer 15

antibiotic leads to permanent loss of replicative ability

Question 16

bacteriostatic

Answer 16

antibiotic leads to temporary loss of growth and replication that returns following removal of antibiotics

Question 17

therapeutic index

Answer 17

ratio of minimum concentration likely to produce an adverse effect to minimum concentration needed to produce a desired effect

wide therapeutic index: safe and effective drug

Question 18

ability to penetrate

Answer 18

delivery of antibiotic to site of infection is most difficult challenge
skin = easy
heart, brain = more difficult (cross BBB)

Question 19

classes of antibiotics

Answer 19

different classes target different parts of replicative cycle and structure (fundamental processes)

cell wall inhibitors
folic acid pathway inhibitors
DNA synthesis inhibitors
protein synthesis inhibitors

Question 20

cell wall inhibitors

Answer 20

penicillin
cephalosporins
beta-lactamase inhibitors
vancomycin

Question 21

penicillin

Answer 21

first antibiotic commercially developed
beta lactams - 4 member ring (also cephalosporins)

inhibit cell wall synthesis by inhibiting DD-transpeptidase (penicillin binding protein)→ cross links components of cell wall = bacteriocidal

work best on gram positive bacteria but increased activity against negative as well

Question 22

beta-lactamase inhibitors

Answer 22

beta-lactamases: bacterial enzymes made by most staphylococci and gram-negative organisms that hydrolyse beta-lactam ring of penicillins, cephalosporins = resistance

beta-lactamase inhibitors: used in combinations to protect hydrolyzable penicillins from inactivation
ex. calvulanic acid

Question 23

vancomycin

Answer 23

inhibits peptidoglycan cross linking (not a beta-lactam)

produced by Actinobacteria species → competition between bacterial species = evolved ways to kill off others

Question 24

folic acid

Answer 24

folic acid is used to synthesize nucleic acids in bacterial DNA
para-aminobenzoic acid (PABA) - precusor for folate in bacteria (eukaryotes pull folic acid from environment)

dihydropteroate synthase converts PABA → dihydrofolic acid
dihydrofolate reductase convers dihydrofolic acid → tetrahydrofolic acid
→ purines → DNA

Question 25

folic acid inhibitors

Answer 25

competitive antagonists that interfere with PABA metabolic pathways by blocking ability of natural substrate to bind

sulfonamides resemble PABA
trimethoprim resembles dihydrofolic acid
usually given together to block sequential steps in synthesis of folic acid

Question 26

protein synthesis

Answer 26

bacteria make protein from mRNA template within the bacterial 70s ribosomal complex
transpeptidation: tRNA transfers an amino acid to the growing amino acid chain

eukaryotes have an 80s ribosomal complex = unaffected by protein synthesis inhibitors

Question 27

protein synthesis inhibitors

Answer 27

block translation of mRNA into protein

chloramphenicol + macrolides: bind to 50s subunit → block transpeptidation

tetracyclines: bind to the 30s subunit → prevent binding of incoming tRNA

aminoglycosides

Question 28

aminoglycosides

Answer 28

bind to 30s ribosomal subunit → block translation in 2 ways
1. block initiation of complex (50s and 30s subunits can’t form complex)
2. cause misreading of code on mRNA template (wrong amino acid is added to peptide chain)
3. inhibit translocation (mature protein can’t be released into extracellular space)

Question 29

antibiotic specificity

Answer 29

selectivity of antibiotics is due to the differences in protein synthesis between humans and bacteria
1. different ribosomal subunits → chloramphenicol does not bind to 80s subunit of mammalian cells
2. mammalian cells cannot synthesize folic acid from PABA

Question 30

bacterial resistance

Answer 30

resistance: ability of microbe to resist effects of antibiotics → consequence of evolution
1. drug inactivation or modification (ex. beta lactamases)
2. alteration of binding site (ex. alteration of penicillin binding proteins → penicillin can no longer bind)
3. alteration of metabolic pathways (ex. using pre-formed folic acid instead of synthesis from PABA)
4. reduced drug accumulation (ex. develop efflux pumps to actively remove antibiotic from cell)

Question 31

gastrointestinal distress

Answer 31

side effect of antibiotic use
altered bacterial environment of the body → loss of normal intestinal flora can cause GI discomfort

mimize effects with probiotic cultures ex. active culture yogurts

Question 32

other side effects

Answer 32

adverse skin reactions
Stevens-Johnson syndrome and toxic epidermal necrolysis → skin becomes detached from underlying tissue