Lecture Set 7 : Part 1 Flashcards
what are antimicrobial drugs?
-compounds that kill (cidal) or inhibit (static) the growth of microorganisms in a human or animal
what must antimicrobial drugs exhibit? what are examples of this?
-selective toxicity
-do damage to the pathogen without harming the host
-ex: peptidoglycan, capsule, 70S ribosome (present in mitochondria)
are most antimicrobial drugs bacteriostatic or bacteriocidal?
-bacteriostatic
-if there is selective pressure on microbes, they develop a resistance
-simply inhibiting the growth instead of killing decreases the pressure
what is the spectrum of activity for antimicrobial drugs?
-range of microbes affected by the drug
-narrow spectrum, very narrow spectrum, or broad spectrum
what is a narrow spectrum of activity?
-affects only microbes within a limited functional group
-ex: penicillin G works against gram positive bacteria only
what is a very narrow spectrum of activity?
-affects only a very specific group of microbes
-ex: isoniazid works against mycobacteria
what is a broad spectrum of activity?
-works against a wide range of microbes from a single domain
-can kill pathogens and non-pathgens (including normal microbiota)
-ex: tetracycline works against both gram positive and gram negative bacteria
what are 2 kinds of synthetic antimicrobial drugs?
-growth factor analogues
-quinolones (fluoroquinolones)
what are growth factor analogues?
-synthetic antimicrobial drugs that are structurally similar to growth factors and interfere with metabolism
-ex: sulfa drugs (sulfanilamide)
-structurally similar to PABA
-inhibits the growth of bacteria by interfering with folic acid synthesis
what are quinolones?
-synthetic antimicrobial drugs that interfere with DNA replication in bacteria
-broad spectrum of activity (DNA is present in all bacteria)
-very effective
-antibiotic resistance develops quickly (DNA is key to survival)
-ex: ciprofloaxacin
-targets an enzyme only used by bacteria, DNA gyrase
-involved in supercoiling DNA (packaging DNA into the nucleoid and during DNA replication)
what are natural antimicrobial drugs?
-antimicrobial agents produced by other microorganisms
-produced to compete with other microbes, NOT to help humans
-NOT for viruses, just for bacteria
-ex: penicillin G (produced by penicillum)
-ex: streptomycin (produced by streptomyces griseus)
how are natural antimicrobial drugs used?
-thousands discovered, but only 1% are clinically useful
-most used today are semi synthetic (natural that has been modified to change its properties)
-ex: penicillin G is acid labile and narrow spectrum, ampicillin is acid stable and broad spectrum
what are B-lactam antibiotics?
-inhibit bacterial cell wall synthesis (excellent selective toxicity)
-contain a B-lactam ring which is the active structural component
-antibiotic resistance has been developed
-ex: penicillins and cephalosporins
how does the b-lactam ring act to inhibit cell wall synthesis?
-binds to periplasmic proteins (penicillin binding proteins) which blocks the final step in synthesis (cross-linking)
how have bacteria developed antibiotic resistance to b-lactam antibiotics?
-some bacteria produce b-lactamase
-enzyme that cleaves the b-lactam ring and destroys the antibiotic
what is methicliin?
-semi synthetic penicillin
-resistant to b-lactamases
-designed to fight multiple antibiotic resistant staphylococcus aureus
-resulted in MRSA (methicillin resistant S. aureus)
what are cephalosporins?
-b-lactam antibiotic that is structurally different from penicillins (still includes the b-lactam ring, same mode of action)
-broader spectrum than penicillins
-more resistant to b-lactamases
-used to treat infections by penicillin resistant gram negative bacteria
what is vancomycin?
-another cell wall synthesis inhibitor
-also blocks the cross-linking, but is structurally different from penicillins
-very narrow spectrum
-active only against some gram positives (including staphylococcus aureus)
-used as first-line treatment against MRSA
why is vancomycin effective against only some gram positives?
-the peptidoglycan is exposed
-the outer membrane of gram negatives protects it from vancomycin
-vancomycin is also a very large molecule (would have a difficult time getting through the outer membrane)
what are examples of protein synthesis inhibitors?
-aminoglycosides
-macrolides
-tetracyclines
why do protein synthesis inhibitors have a lower selective toxicity?
-the ribosome subunits of bacteria can be found in the mitochondria of human/animal cells
what are aminoglycosides?
-amino sugars linked by glycosidic bonds
-target the 30S subunit of the ribosome (able to fully block protein synthesis)
-act in an irreversible fashion, once they bind, they dont unbind
-broad spectrum, but particularly useful against gram negative bacteria (smaller molecule)
-last resort antibiotic (can be toxic towards humans)
-ex: streptomycin (produced by streptomyceis griseus)
what are macrolides?
-have a structure based on the lactone ring (substitutions to this ring can make macrolides with different properties)
-ex: erythromycin (produced by streptomyces erytherus)
-targets the 50S subunit of the ribosome (partially blocks protein synthesis )
-leads to preferential synthesis of some proteins
-narrow spectrum against gram positives
-large hydrophobic molecule does not penetrate the outer membrane of gram negatives
what are tetracyclines?
-produced by streptomyces aureofaciens (and several other streptomyces species)
-inhibits the 30S subunit of the ribosome (fully blocks protein synthesis)
-broad spectrum
-one the most heavily used antibiotics
-used extensively in agriculture as well
-overuse has led to a resistance
