Micro Ch. 18

Front 1

Antimicrobial Chemotherapeutic Agents:
1. Desirable properties of antimicrobial agents
What makes a good antimicrobial chemotherapeutic agent?

Back 1

Selective toxicity

Front 2

Selective toxicity

Back 2

kills microbes, but minimal damage to host
Measurement of selective toxicity:
• Minimum effective dose for 50% of the population = ED50
• Lethal dose of a drug for 50% of the population = LD50

Front 3

Therapeutic index

Back 3

LD50 / ED50

Can go from 2 to 100
• The index better the chemotherapeutic higher the index, the agent

As few side effects as possible – undesirable consequences to the host

Front 4

Common bacterial cell targets of antibiotics:

Back 4

Common bacterial cell targets of antibiotics:
• Biochemical pathways unique to certain pathogens
• Prokaryotic transcription or translation (ribosomes)
• Peptidoglycan synthesis
• Prokaryotic cell membrane permeability

Front 5

Paul Ehrlich

Back 5

originally discovered in 1896 but forgotten;
rediscovered in 1929 by Alexander Fleming, who
found that Penicillium produced the substance;
1939 – penicillin finally purified by two Oxford scientists

• Streptomycin: 1944; chloramphenicol, neomycin,
terramycin, tetracycline: 1953

Front 6

Chemotherapeutic agents

Back 6

chemical compounds that can be used internally for control of infectious diseases

-synthetic agents and antibiotics

Front 7

synthetic agents

Back 7

synthetic growth factor analogs that
inhibits a necessary step in a microbial metabolic pathway y p p

Front 8

antibiotics

Back 8

natural chemical compound products that
inhibit or kill microorganisms

Front 9

Narrow spectrum antibiotics

Back 9

inhibit or kill only select bacteria

Front 10

Broad spectrum antibiotics

Back 10

effective against a wider range of bacteria

Front 11

Antibiotics: Inhibitors of important microbial cellular processes
modes of action

Back 11

A. Inhibition of a critical pathway
B. Inhibition of DNA/RNA synthesis
C. Inhibition of cell wall synthesis
D. Inhibition of protein synthesis
E. Alteration of cell membranes

Front 12

Growth factor analog

Back 12

synthetic compound that is structurally similar
to a growth factor but slight differences make
it not work in the cell

Front 13

Analogs are known for many important biomolecules:

Back 13

(vitamins, amino
acids, purines, and pyrimidines)

Front 14

Sulfa Drugs

Back 14

inhibitors of folic acid biosynthesis

Front 15

Sulfanilamide is an analog of:

Back 15

an analog of p-aminobenzoic acid

Front 16

Mode of action of sulfanilamide:

Back 16

Inhibits the
incorporation of p- aminobenzoic acid into the
vitamin folic acid → bacteria
are no longer able to make
folic acid

Front 17

Bacteria synthesize their own
folic acid – most animals get
folic acid only from their ___

Back 17

diet

Front 18

Sulfa drugs are selective
agents against ____.

Back 18

bacteria

Front 19

____ is a lipid that complexes with
peptidoglycan in the cell wall of Mycobacteria

Back 19

Mycolic acid

Front 20

Isoniazid

Back 20

an analog of nicotinamide, a
precursor of mycolic acid

most effective single drug for the
treatment of tuberculosis

ex. narrow spectrum antibiotic

Front 21

Bacterial DNA gyrase supercoiling
is responsible for

Back 21

DNA to help packaging in the bacterial cell

Front 22

Fluoroquinolone drugs interfere with

Back 22

DNA gyrase

Front 23

Because DNA gyrase is found in Gram-negative and gy g
Gram-positive bacteria, ______can be
used to treat both types of infections

Back 23

Fluoroquinolones

Front 24

Ciprofloxacin (= Cipro) is used to treat:

Back 24

urinary
infections and anthrax

Front 25

____ are antimicrobial agents produced by microbes

Back 25

Antibiotics

Front 26

function of antibiotics

Back 26

Function:
microbial chemical warfare. Microbes in the same environment compete for
the same nutrients. They gain a strong advantage by inhibiting or killing other species

Front 27

The ____ antibiotics inhibit cell wall synthesis

Back 27

β-lactam

Front 28

β-lactam antibiotics get their name from their____.

Back 28

β-lactam ring

Front 29

first β-lactam antibiotic
discovered and produced commercially

Back 29

Penicillin G

Front 30

Penicillin G is Effective mainly against:

Back 30

Gram+ organisms
(Gram- are impermeable to penicillin G)

Front 31

Penicillin G mode of action:

Back 31

prevent transpeptidase
reaction the enzyme = inhibit
β-ring by binding to peptidoglycan synthesis

Front 32

Transpeptidases are also known as

Back 32

penicillin-binding proteins

Front 33

Penicillin-transpeptidase complex
stimulates

Back 33

release of autolysins by bacteria.
Autolysins degrade the existing cell wall

Front 34

Bacteria that produce the enzyme β-lactamase
are resistant to

Back 34

penicillin

Front 35

Some penicillin semisynthetic derivatives are

Back 35

resistant to β-lactamase

Front 36

Cephalosporins

Back 36

also β-lactam antibiotics
and act in the same way as penicillins

more resistant to β-lactam

Front 37

Vancomycin

Back 37

not a β-lactam antibiotic,
peptidoglycan but binds to precursors to
prevent cell wall synthesis.
Used to treat penicillin-resistant bacteria

Front 38

Aminoglycosides:

Bind to the:

Back 38

Made of amino sugars linked by
glycosidic bonds

Bind to the 30S subunit of the ribosome

Front 39

Mode of bacterial resistance for Aminoglycosides:

Back 39

modification of the drug
by an “N-acetyltransferase” enzyme → inactive form

Front 40

Because of serious side-effects and bacterial resistance, aminoglycosides are only used as:

Back 40

reserve antibiotics when others fail

Front 41

Tetracyclines in hibit:

Back 41

Inhibit almost all Gram- and Gram+
bacteria

Front 42

Tetracyclines bind to the:

Back 42

Bind to the 30S subunit of the ribosome

Front 43

Many different tetracyclines are produced _____.

Back 43

semisynthetically

Front 44

Have been widely used in the past an nutritional
supplements for swine and poultry

Back 44

Tetracyclines

Front 45

Tetracyclines are Produced by ____ species

Back 45

Streptomyces

Front 46

Macrolides:

They bind to:

Back 46

Contain lactone rings linked to sugars

Bind to the 50S subunit of the ribosome

Front 47

Macrolides are Best known is

Back 47

erythromycin

Front 48

Macrolides target a broad spectrum of:

Back 48

Target a broad spectrum of bacteria

Front 49

Macrolides are commonly used:

Back 49

Commonly used for patients allergic to penicillins

Front 50

Marcrolides are produced by:

Back 50

Produced by Streptomyces species

Front 51

Daptomycin

Example:

Back 51

A cyclic lipopeptide natural product
from certain Streptomyces species

“ionophore” antibiotic

Front 52

Daptomycin binds to:

Back 52

Binds to bacterial cytoplasmic membranes, forms
pores, resulting in depolarization of the membrane
→ death
no energy → cell

Front 53

Daptomycin has rare instances of:

Back 53

Rare instances of resistance

Front 54

Monensin

Back 54

an ionophore used in animal feed

Front 55

Platensimycin

produced by:

Back 55

Inhibits enzyme involved in fatty acid
(and membrane) biosynthesis; produced by
Streptomyces platensis

Front 56

Plantensimycin is effective against:

Back 56

Effective against many Gram+ bacteria, including
methicillin and vancomycin-resistant species

Front 57

Plantensimycin has no know potential for development of:

Back 57

resistance
by pathogens

Front 58

Acquired antibiotic drug resistance

Back 58

acquired ability of a microbe to resist the effect of a drug to which it is initially susceptible

Front 59

Methods of antibiotic resistance used by bacteria:

Back 59

1 A particular taget (binding site or enzyme) may be lacking in the organism
2. Organisms may be impermeable to the drug
3. Modification of the antibiotic to an inactive form
4. Target of the antibiotic may be altered
5. Mutation that results in a metabolic bypass around a step blocked by an antibiotic
6. The organism can pump the antibiotic out of the bacterium with an efflux pump

Front 60

Role of plasmids in microbial antibiotic resistance:
Plasmids encode antibiotic resistance enzymes and proteins = _____. R plasmids originated before clinical use of many antibiotics

Back 60

“R” (resistance)
plasmids.

Front 61

Why are antibiotic resistant strains of pathogenic organisms more prevalent today?

Back 61

Use of antibiotics creates great selective pressure favoring microbes that are
resistant to the drug and selecting against microbes that are sensitive to the drug
• Overuse of antibiotics results in increased prevalence of drug-resistant strains p g
within human populations
• Antibiotics are also used as additives in agricultural settings for animal feeds, fish
farming, and even fruit production

Front 62

Inclusion of fluoroquinolone (FQ) in
animal feed can lead to increased
prevalence of ____ in humans

Back 62

FQ-resistant
Campylobacter

Front 63

clinical trial system

Back 63

for new drug approval the clinical trial system by Food and Drug
Administration (antimicrobials and all other drugs must go through this process)

Front 64

clinical trial system process:

Back 64

drug discovery
phase I trials
phase II trials
phase III trials
FDA approval
post marketing/phase VI
discovery to maket: 20-25 years

Front 65

toxicity

Back 65

Most antiviral drugs also affect the host cell

Front 66

Reverse transcriptase inhibitors: Most successful agents against the _____

Back 66

AIDS virus

Front 67

Nucleoside reverse transcriptase inhibitors

Back 67

Useful against retroviruses (viruses with
RNA genome); block the RNA → DNA step
catalyzed by reverse transcriptase; get
incorporated into the newly formed DNA and
block the next step

Front 68

Non-nucleoside reverse transcriptase inhibitors

Back 68

Bind directly to the reverse transcriptase to block the RNA → DNA step

Front 69

Protease inhibitors:

Effective for the treatment of:

Back 69

Prevent cleavage of
important proteins required for viral replication
• Effective for the treatment of HIV, bind to the
HIV protease

Front 70

Fusion inhibitors

Back 70

prevent entry of the
into the virus cell
• Enfuvirtide, binds to the HIV gp41
membrane protein

Front 71

Neuraminidase inhibitors

Back 71

prevent virus
release from infected cells [Tamiflu, Relenza]

for influenza only

Front 72

Recent therapies for HIV treatment

Back 72

Recent therapies for HIV treatment:
Multi-drug combinations – use of 2-3
different drugs at once has a more
beneficial Combivir® = Lamivudine + Zidovudine
( = effect than each drug alone
e.g., AZT + protease inhibitors
3TC + AZT)
Combined antiviral drugs improve
efficiency of AZT therapy

Front 73

Because fungi are ____, they share a lot of their cellular machinery
with
with animals and humans → many antifungal drugs have toxic side-

Back 73

eukaryotes

Front 74

a few drugs target unique fungal structures or metabolic processes =

Back 74

they are selectively toxic for fungi only

Front 75

Ergosterol inhibitors:
Ergosterol:

Back 75

sterol present the cytoplasmic in membrane of fungi, instead of cholesterol

Front 76

Two types of ergosterol inhibitors

Back 76

1. Bind to ergosterol; cause membrane
permeability and cell death
2. Inhibit ergosterol biosynthesis

Front 77

Inhibitors of cell wall synthesis

Back 77

1,3 β-D glucan synthase forms glucan polymers in fungal cell walls; animal
cells do not have cell walls or 1,3 β-D glucan synthase
β f • Echinocandins inhibit 1,3 β-D glucan synthase, resulting in fungal cell death
• Polyoxins: inhibitors of chitin biosynthesis (used as agricultural fungicides)

Front 78

Echinocandins inhibit:

Back 78

1,3 β-D glucan synthase, resulting in fungal cell death

Front 79

Polyoxins

Back 79

inhibitors of chitin biosynthesis (used as agricultural fungicides)

Front 80

desirable properties of antimicrobial agents

Back 80

as few of side effects as possible
selective toxicity

Front 81

inhibitors of folic acid

Back 81

sulfa drugs

Front 82

cell wall inhibitor (example)

Back 82

mycolic acid

Front 83

inhibitors of DNA packaging

Back 83

Fluoroquinolone

Front 84

antibiotics that inhibit protein synthesis

Back 84

Aminoglycosides
Tetracyclines
Macrolides

Front 85

antibiotics interfering with cell membrane properties

Back 85

Daptomycin
Platensimycin