Lecture 11: Antimicrobial Drugs and Drug Resistance

Question 1

______: Used when immunization has not occurred and the immune system has
difficulty to eliminate infection

Answer 1

antimicrobial drugs

Question 2

______: are useful against bacterial infection, when very few antivirals are available

Answer 2

antimicrobial drugs

Question 3

T/F: antimicrobial drugs must display selective toxicity or they will cause damage to the host

Answer 3

true!

Question 4

what are the two broad categories of antimicrobial drugs?

Answer 4

synthetic and natural

Question 5

T/F: synthetic antimicrobials are better than natural

Answer 5

false! natural are always better at what they do

Question 6

T/F: Large number of naturally occurring antibiotics with no clinical use

Answer 6

true! there are so many antibiotic producing organisms

Question 7

antimicrobial drugs can be… Bacteriostatic or bacteriocidal, what is the difference?

Answer 7

Bacteriostatic- stops growth
bacteriocidal- kills

Question 8

antimicrobial drugs can be… Broad spectrum or narrow spectrum, what is the difference?

Answer 8

Broad spectrum- covers all bases but destroys everything with thing it targets
narrow spectrum- specific and tailored to specific microbe

Question 9

T/F: Cell wall active agents offer excellent selective toxicity

Answer 9

true! most widely used class of antibiotics… because eukaryotic cells dont have cell walls! doesn’t target us!

Question 10

largest class of cell wall active antimicrobial drugs are _____

Answer 10

beta lactam antibiotics

Question 11

_______ antibiotics:
Common feature is the b-lactam ring
* Naturally occurring: produced by Penicillium and Cephalosporium fungi
* Example: penicillins and cephalosporins
* Can be modified in the lab to produce semi-synthetic drugs that have a
modified spectrum of activity
* Susceptible to beta-lactamases
* Enzyme produced by some bugs to cut and inactivate beta-lactams

Answer 11

beta lactam antibiotics

Question 12

who produces beta lactam antibiotics?

Answer 12

Penicillium and Cephalosporium fungi

Question 13

T/F: shape of beta lactam ring will affect where it works/functions

Answer 13

true!

Question 14

what are semi-synthetic antibiotics?
how are beta lactam antibiotics altered?

Answer 14

naturally occuring antibiotics that have been altered to resist the things that destroy them…
by adding a big blocker to beta lactam ring, can prevent beta lactamase from cutting its cut site and destroying antibiotic!

Question 15

T/F: Penicillins have a narrow spectrum of
activity

Answer 15

true!

Question 16

______: Characterized by a five membered ring
attached to the beta-lactam component

Answer 16

penicillins

Question 17

what do penicillins target?

Answer 17

transpeptidation in gram positive bacteria

Question 18

T/F: penicillins Cannot penetrate outer membrane of gram negative bacteria

what has been done to combat this?

Answer 18

true!

Semi-synthetic penicillin are modified
to provide some activity against gram
negative bugs

Question 19

_____: Structurally distinct from penicillins
* Six membered ring is attached to the beta-lactam component

Answer 19

cephalosporins

Question 20

what do cephalosporins target?

Answer 20

also target transpeptidation of peptidoglycan, like penicillin!

doesn’t allow peptidoglycan to be cross-linked, alters strength

Question 21

T/F: Better resistance against beta lactamases than penicillin

Answer 21

true!

Question 22

T/F: Broader spectrum of activity than penicillin

Answer 22

true!

Question 23

which antibiotic is grouped into generations?

Answer 23

cephalosporins

1st gen, 2nd gen, etc.

Question 24

cephalosporins are _____, they can’t kill fully formed cells because they can only target cell wall while its actively being built… meaning number of bacteria will stay the same

Answer 24

bacteriostatic

Question 25

Growth factor analogs are structurally similar to growth factors but do not _________

Answer 25

function in the cell

Question 26

_______: Inhibit growth of bacteria by inhibiting folic acid synthesis and thus nucleic acid synthesis

Answer 26

sulfa drugs screws over their replication! can't make proteins or nucleotides!

Question 27

why is the selectivity of sulfa drugs so good?

Answer 27

they target things we don't have... so they're great at what they do!

Question 28

sulfa drugs are fully _______

Answer 28

synthetic

Question 29

sulfa drugs are often used in combination with another analog... why?

Answer 29

Combination therapy minimizes the likelihood of resistance, overwhelming bug so that chance it avoids everything is almost non-existant

Question 30

_______: Extremely narrow spectrum cell wall active agent * Analog of mycolic acid component needed by Mycobacterium spp

Answer 30

isoniazid

Question 31

________: * Synthetic antimicrobials inhibit DNA gyrase

Answer 31

Quinolones

Question 32

quinolones inhibit DNA gyrase, what does DNA gyrase do? why is it such a perfect target?

Answer 32

Prevents supercoiling of DNA, enzyme is only used in DNA replication in bacteria... doesn't target us at all!

Question 33

quinolones are active against both.... bacteria

Answer 33

gram negative and gram-positive making it broad spectrum!

Question 34

ciprofloxacin is a _______ that is useful against life threatening infections

Answer 34

fluorinated quinolone (fluoroquinolone)

Question 35

Protein synthesis inhibitors target _____ ribosomes

Answer 35

70S

Question 36

why are there some risks with using protein synthesis inhibitors?

Answer 36

they target 70S ribosomes, which we have in our mitochondrial matrix.. but its pretty hard to get that far in the cell so we can still use PSI

Question 37

_______: Bind to the 30S subunit of 70S ribosomes * Block translation * Narrow spectrum * Useful against gram negative bugs * Often used as a last resort drug * Damaging to the kidneys and ears * Examples include streptomycin, gentamycin and neomycin

Answer 37

aminoglycosides

Question 38

examples of aminoglycosides include... (three)

Answer 38

streptomycin, gentamycin and neomycin

Question 39

why are aminoglycosides used as a last resort drug?

Answer 39

damaging to kidneys and ears... only used if patient has no other option

Question 40

what are the three types of protein synthesis inhibitors?

Answer 40

aminoglycosides, tetracycline, macrolides

Question 41

_______: Broad spectrum * Produced by species of the Streptomyces genus * Bind to the 30S subunit * Consist of both natural and modified semisynthetic drugs * Binds to calcium damaging teeth and bone * Shouldn’t be used in children and pregnant women * Used in veterinary medicine and to promote animal growth * Creates problems with resistance

Answer 41

tetracycline

Question 42

who produces tetracycline?

Answer 42

species of Streptomyces

Question 43

why are tetracycline drugs used to promote animal growth?

Answer 43

competitive bacteria are removed, animals can grow more since they arent competing for nutrients

Question 44

______: Broad spectrum of activity * Bind to the 50S ribosomal subunit * Only inhibits translation of some proteins * Some proteins are preferential translated and others are not * Creates a detrimental protein imbalance inside of the cell * Useful to treat infection in patients with allergies to beta lactam antibiotics * Example: erythromycin and azithromycin * Produced by Streptomyces spp.

Answer 44

macrolides

Question 45

how do macrolides work?

Answer 45

they create detrimental protein imbalances by binding to 50S ribosomal subunit puts cell in trouble!!

Question 46

when are macrolides used to treat infection in place of another antibiotic? (allergies!)

Answer 46

Useful to treat infection in patients with allergies to beta lactam antibiotics (ex: penicillin)

Question 47

what are two examples of macrolides

Answer 47

erythromycin and azithromycin

Question 48

Daptomycin is a _____

Answer 48

novel antibiotic

Question 49

who produces Daptomycin

Answer 49

streptomyces

Question 50

Daptomycin is a cyclic lipopeptide, and is active against ____

Answer 50

gram-positives

Question 51

how do Daptomycin work?

Answer 51

Forms pores in the plasma membrane causing depolarization * Cell cannot synthesize necessary biomolecules * Cell death occurs

Question 52

are daptomycin bacteriostatic or bacteriocidal

Answer 52

bacteriostatic, they poke holes.. don't lyse... so they're not outright killing bacteria

Question 53

when does daptomycin resistance occur? how?

Answer 53

Resistance can occur when bacteria alter plasma membrane composition... since bacteria can change their composition so much easier than us (we pretty much can't!)

Question 54

Platensimycin is a _____

Answer 54

novel antibiotic

Question 55

______: Inhibits fatty acid biosynthesis * Produced by Streptomyces platensis * Broad spectrum of activity against gram positive bacteria * Useful against important resistant gram positive pathogens * MRSA and VRE * Does not cause toxicity in the host

Answer 55

platensimycin

Question 56

who produces Platensimycin

Answer 56

streptomyces Platensis

Question 57

T/F: Platensimycin does not cause toxicity in the host

Answer 57

true! useful against important resistant gram positive pathogens

Question 58

______ occurs when an organism develops a mechanism to elude the activity of an antimicrobial drug that it should otherwise be susceptible to

Answer 58

Antibiotic resistance

Question 59

T/F: Genes for antibiotic resistance can either be encoded on a plasmid or directly within the genome

Answer 59

true!

Question 60

how does antibiotic resistance occur?

Answer 60

through random mutation

Question 61

Resistance is prevalent because of widespread and sometimes incorrect use of antibiotics... in what three sectors?

Answer 61

medicine (handed out to humans too often, not taken properly) veterinary med (given too much to animals) agriculture (antibiotic runoff into drinking water)

Question 62

what five mechanisms can bacteria use to become resistant to antibiotics?

Answer 62

reduce permeability (shut out antibiotic) inactivation of antibiotic alternation of taregt (change binding site through randome mutation) development of resistant biochemical pathway efflux (let in antibiotic, then kick it out)

Question 63

T/F: Emergence of antibiotic resistance in gram negatives is super prevalant (more than gram positive)

Answer 63

true! many types of bacteria are becoming increasingly resistant but lots of them are gram negative !!

Question 64

what four ways can we prevent antibiotic resistance?

Answer 64

Infection prevention Rapid and conclusive diagnosis Appropriate/prudent use of antibiotics Prevention of transmission

Question 65

how do we use patterns of antimicrobial resistance to our advantage?

Answer 65

we try to anticipate the next big breakout! stay on top of mutations best we can (pretty much impossible)