Transcript Microbiology

Antimicrobial Drugs
 Chemotherapy: the use of drugs to treat a disease
 Antimicrobial drugs: interfere with the growth of
microbes within a host
 Antibiotic: a substance produced by a microbe
that, in small amounts, inhibits another microbe
 Selective toxicity: killing harmful microbes without
damaging the host
Antimicrobial Drugs
 1928: Fleming discovered penicillin, produced
by Penicillium
 1940: Howard Florey and Ernst Chain performed
first clinical trials of penicillin
Figure 20.1 Laboratory observation of antibiosis.
Table 20.1 Representative Sources of Antibiotics
Insert Table 20.1
The Spectrum of Antimicrobial Activity
 Broad spectrum
 Narrow spectrum
 Superinfection
Table 20.2 The Spectrum of Activity of Antibiotics and Other Antimicrobial Drugs
The Action of Antimicrobial Drugs
 Bactericidal
 Kill microbes directly
 Bacteriostatic
 Prevent microbes from growing
Figure 20.3 The inhibition of bacterial cell synthesis by penicillin.
Rod-shaped bacterium before
penicillin.
The bacterial cell lysing as
penicillin weakens the cell wall.
Figure 20.4 The inhibition of protein synthesis by antibiotics.
Protein
synthesis
site
Growing
polypeptide
Tunnel
Growing polypeptide
50S
5′
Chloramphenicol
Binds to 50S portion and
inhibits formation of
peptide bond
30S
mRNA
50S
portion
3′
Three-dimensional detail of the protein
synthesis site showing the 30S and 50S
subunit portions of the 70S prokaryotic
ribosome
Messenger
RNA
Streptomycin
Changes shape of 30S portion,
causing code on mRNA to be
read incorrectly
Protein synthesis site
tRNA
30S portion
Direction of ribosome movement
Tetracyclines
70S prokaryotic
ribosome
Translation
Interfere with attachment of
tRNA to mRNA–ribosome
complex
Diagram indicating the different points at which chloramphenicol,
the tetracyclines, and streptomycin exert their activities
Figure 20.5 Injury to the plasma membrane of a yeast cell caused by an antifungal drug.
Table 20.3 Antibacterial Drugs (Part 1 of 3)
Table 20.3 Antibacterial Drugs (Part 2 of 3)
Table 20.3 Antibacterial Drugs (Part 3 of 3)
Figure 20.2 Major Action Modes of Antimicrobial Drugs.
1. Inhibition of cell wall synthesis: penicillins,
2. Inhibition of protein synthesis: chloramphenicol,
cephalosporins, bacitracin, vancomycin
erythryomycin, tetracyclines, streptomycin
DNA
mRNA
Transcription
Protein
Translation
Replication
Enzyme
4. Injury to plasma
membrane:
polymyxin B
5. Inhibition of essential
metabolite synthesis:
sulfanimide, trimethoprim
3. Inhibition of nucleic acid replication
and transcription: quinolones, rifampin
Tests to Guide Chemotherapy
 MIC: minimal inhibitory concentration
 MBC: minimal bactericidal concentration
 Antibiogram
Figure 20.17 The disk-diffusion method for determining the activity of antimicrobials.
Figure 20.18 The E test (for epsilometer), a gradient diffusion method that determines antibiotic
sensitivity and estimates minimal inhibitory concentration (MIC).
MIC
MIC
Figure 20.19 A microdilution, or microtiter, plate used for testing for minimal inhibitory concentration
(MIC) of antibiotics.
Doxycycline
(Growth in all wells, resistant)
Sulfamethoxazole
(Trailing end point; usually read where there
is an estimated 80% reduction in growth)
Streptomycin
(No growth in any well; sensitive at all
concentrations)
Ethambutol
(Growth in fourth wells;
equally sensitive to
ethambutol and kanamycin)
Kanamycin
Decreasing concentration of drug
Figure 20.21 The development of an antibiotic-resistant mutant during antibiotic therapy.
Bacteria (number/ml)
Initiation of
antibiotic therapy
108
50
107
40
106
30
Bacteria
count
105
20
104
10
103
0
1
2
3
4
5
6
Days
7
8
9
10
11
Antibiotic resistance (mg/ml)
Antibiotic resistance of bacterial
population measured by amount of
antibiotic needed to control growth
Antibiotic Resistance
 A variety of mutations can lead to antibiotic
resistance
 Resistance genes are often on plasmids or
transposons that can be transferred between
bacteria
Antibiotic Resistance
 Misuse of antibiotics selects for resistance mutants
 Misuse includes:
 Using outdated or weakened antibiotics
 Using antibiotics for the common cold and other
inappropriate conditions
 Using antibiotics in animal feed
 Failing to complete the prescribed regimen
 Using someone else’s leftover prescription
Figure 20.20 Bacterial Resistance to Antibiotics.
1. Blocking entry
Antibiotic
2. Inactivation by enzymes
Antibiotic
Antibiotic
Altered target
molecule
Enzymatic action
3. Alteration of target molecule
4. Efflux of antibiotic
Inactivated
antibiotic
Resistance
plasmid
S. enterica
after conjugation
S. enterica
Cephalosporin-resistance in E.
coli transferred by conjugation
to Salmonella enterica in the
intestinal tracts of turkeys.
E. coli
Clinical Focus Antibiotics in Animal Feed Linked to Human Disease, Figure A.
Clinical Focus Antibiotics in Animal Feed Linked to Human Disease, Figure B.
Flouroquinolone-resistant Campylobacter jejuni in the United States, 1986–2008.
Percent FQ-resistant Campylobacter
30
FQ for
humans
FQ for
poultry
FQ for poultry
discontinued
25
20
15
10
5
0
1986
1988
1990
1992
1994
1996
1998
Year
2000
2002
2004
2006
2008
Effects of Combinations of Drugs
 Synergism occurs when the effect of two drugs
together is greater than the effect of either alone
 Antagonism occurs when the effect of two
drugs together is less than the effect of either
alone
Figure 20.23 An example of synergism between two different antibiotics.
Area of synergistic
inhibition, clear
Disk with antibiotic
amoxicillin-clavulanic
acid
Area of growth,
cloudy
Disk with antibiotic
aztreonam