Antibiotics Flashcards
What are antibiotics? And 2 kinds?
Soluble compounds produced/released by microorganisms that inhibit growth/kill other microorganisms (bacteria for competition); synthetic and semi-synthetic
What are bacteria? (2)
Single cell organisms that are of the first life forms on Earth
What 4 habitats can bacteria be found in?
found in soil, water, acidic hot springs, Earth’s crust
What relationship do bacteria have w/ plants and animals?
symbiotic and parasitic relationship w/ plants and animals
Where are symbiotic bacteria found?
GI tract
What are 3 criteria for bacteria classification?
Aerobic/anaerobic, shape (rod, sphere, spiral, etc), cell wall
What are the names for rod and sphere shapes in bacteria?
Rod: bacillus (streptobacillus- chain)
Sphere: coccus (streptococcus-chain)
What are 2 types of bacterial cell walls?
Gram - (pink) and + (purple)
What is diff btwn cell walls of gram -/+ bacteria?
+: many layers of peptidoglycan (thick)
-: few layers of peptidoglycan (thin) w/ outer lipid memb (lipopolysacch and lipoproteins)
What are bacterial cell walls made of?
peptidoglycan (polysacch)
What causes the diff colours fo gram +/- bacteria?
Gram stain colours peptidoglycan purple
+: purple (outer peptidoglycan layers)
-: pink (lipid memb protects peptidoglycan)
What kind of cell wall do most bacteria have?
Gram - (lipid layer around peptidoglycan)
What is the structure of peptidoglycan?
Glycan strands w/ alternating N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) residues cross linked by peptides
What enzyme polymerizes individual strands of peptidoglycan chain?
Glycosyltransferase (GT)
What enzyme cross links peptidoglycan strands?
Transpeptidase (TP)
T/f: transpeptidase is targeted by antibiotics (penicillin binding protein)
True
What are normal flora?
Microbial species that cover our bodies (skin, mouth, lg intestine, and genitals)
When does normal flora cause problems? (2)
Immune system is weakened, gain access to normally sterile areas (perforated bowel)
T/f: pathogens require host to be immune-compromised/injured for infection
False, dont require host to be immune compromised/injured for infection
What are 4 diseases caused by pathogenic bacteria?
Food borne illnesses, STIs, skin infections, highly infectious diseases
T/f: prior to 1930/40s, it was common for otherwise healthy individuals to die from bacterial infections that are considered commonplace/non threatening
True
What antibiotics were developed in 1930s vs 1940s?
1930: sulfonamides
1940: penicillins
What does antibiotic “spectrum of activity” mean? And 2 types?
Range of bacterial species the antibiotic targets; narrow and broad
What does antibiotic “bacterial sensitivity” mean? 2 types?
Measures antibiotic ability to kill or prevent replication of bacteria;
bactericidal and bacteriostatic
What’s the difference btwn bacteriocidal vs bacteriostatic antibiotics?
Bacteriocidal: causes permanent loss of bacteria’s replicative ability
Bacteriostatic: causes temporary loss of bacteria’s growth and replication which returns after antibiotic removal
What does antibiotic “therapeutic index” mean?
Ratio of min conc needed to produce and adverse effect: min conc for desired effect (bigger is better)
What is an antibiotics “ability to penetrate” mean?
Bioavailability/ability of antibiotic to reach the site of infection
What is the most difficult challenge of antibiotic delivery?
Ability to penetrate
What are 4 classes of antibiotics?
Cell wall inhibitors, folic acid inhibitors, DNA synthesis inhibitors, protein synthesis inhibitors (pathways are diff to euk cells)
What is penicillin derived from?
Penicillium notatum
What is an ex of a cell wall inhibitor?
Penicillin
Who and when was penicillin discovered?
Alexander Fleming in 1928
What was the first antibiotic commercially developed?
Penicillin
What are cephalosporins derived from?
Acremonium fungus
What are penicillins and cephalosporins called? Why?
Beta lactams; have 4 membered ring
What do beta-lactams do? (Penicillin and cephalosporins)
Inhibit cell wall synthesis by inhibiting DD transpeptidase that cross-links components of cells walls
Are beta-lactams (penicillin and cephalosporins) considered bacteriocidal or bacteriostatic?
Bacteriocidal (inhibit cell wall synth-cause cell death)
What is DD transpeptidase aka?
Penicillin binding protein
What were cell wall inhibitors originally most effective against?
Gram positive (peptidoglycan on outside) but can work on gram - but less effectively
What are beta-lactamases?
Bacterial enzymes (penicillinases, cephalosporinases) that hydrolize beta-lactam ring of penicillins and cephalosporins
What are beta-lactamases made by (2) and confer?
Staphylococci and other gram - organisms; confers resistance
What are beta-lactamase inhibitors? When are they used?
Potent inhibitors of beta-lactamases used w/ penicillins to protect from hydrolysis/inactivation
What is vancomycin? What makes is different?
Cell wall inhibitor; not a beta-lactam
How does vancomycin work?
Inhibits peptidoglycan cross linking
What produces vancomycin in nature? Ex?
Actinobacteria species; Amycolatopsis orientalis in soil
Why would bacteria make antibiotics?
For competition against other bacteria
Why are folic acid inhibitors good antibiotics?
Bcse bacteria use folic acid to synthesize nucleic acids for DNA
What is para-aminobenzoic acid (PABA)?
Precursor to folate in bacteria obtained from enviro
T/f: euk also use folic acid to build folic acid, but it is obtained from diet not synthesized from PABA
True, only bacteria use PABA pathway for folic acid synthesis
What are 2 folic acid inhibitors? How do they work?
Sulfonamides and trimethoprim; interfere w/ PABA pathway to sequentially inhibit folic acid synthesis when used together
What do sulfonamides and trimethoprim resemble respectively?
Sulfonamides: PABA
Trimethoprim: dihydrofolic acid
How does using sulfonamides and trimehtoprim inhibit folic acid synthesis?
Competes w/ PABA and dihydrofolic acid for enzyme, respectively
What are 3 protein synthesis inhibitors?
Chloramphenicol, tetracyclines, macrolides
Where do bacteria make proteins from mRNA?
70s ribosomal complex
What transfers aa to the growing peptide chain in bacteria?
tRNA (t6)
What is the process of adding aa to growing peptide chain in bacteria called?
Transpeptidation
What ribosomal complex do euk have? Benefit?
80s; are unaffected by protein synthesis inhibitors
What 2 antibiotic drugs bind to the 50s subunit of the 70s ribosome?
Chloramphenicol and macrolides
What antibiotics bind to the 30s subunit of the 70s ribosome?
Tetracyclines
What is the difference in mech of action btwn chloramphenicol/macrolides and tetracyclines?
(Both inhibit protein synthesis)
Chlor/macrolides: block transpeptidation
Tetracyclines: prevent binding of incoming tRNA
What is another antibiotic that binds to the 30s subunit but blocks protein synthesis in 3 ways?
Aminoglycosides
What 3 ways do aminoglycosides inhibit protein synthesis?
- Block joining of ribosomal subunits
- Misreading of mRNA template
- Block translocation (protein release from ribosome)
Why dont protein synthesis inhibit human cells as well?
Difference in enzyme specificity btwn bacteria vs euk, diff shape of ribosome (70s vs 80s), diff metabolic pathways (PABA to folic acid)
What is the most common antibiotic side effects?
Bacterial resistance
What is bacterial resistance?
Ability of microbe to resist effects of antibiotics as a consequence of natural selection (mutation that allows survival will persist)
What 4 ways can bacteria develop resistance? And ex (already discussed)?
- Drug inactivation/modification (beta-lactamases)
- Alteration of binding site (penicillin binding proteins-transpeptidases)
- Alteration of metabolic pathways (retrieve PABA from enviro to avoid synthesis)
- Reduced drug accumulation (efflux pumps to remove antibiotic from cell)
How do antibiotics affect the GI tract causing distress? Effect?
Alters bacterial enviro (normal flora) which causes diarrhea or discomfort
What can minimize GI effects of antibiotics?
Probiotics (active culture in yogurts)
What is another (not GI) side effect of antibiotics? Prevention?
Adverse skin runs (mild rash to photo sensitivity); sunscreen
What are Stevens-Johnsons syndrome and toxic epidermal necrolysis?
Rare conditions where skin becomes detached from underlying tissues and sloughs off body (can be lethal)