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"igure 20%#2 The structure of the antibacterial antibiotic erythromycin( a representative macrolide%
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igure 20%#2 The structure of the antibacterial antibiotic erythromycin( a representative macrolide%
>rythromycin
:acrocycliclactone ring
h b f h
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Chec 1our nderstanding+hy does erythro#ycin, a #acrolide antibiotic,ha(e a spectru# of acti(ity li#ited largely togra#-positi(e bacteria e(en though its #ode ofaction is si#ilar to that of the broad-spectru#tetracyclines 20-;
f the three drugs often found in o(er-the-
counter antiseptic crea#sFpoly#y!in
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ulfonamides +sulfa drugs,Inhibit folic acid synthesis
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Action of >n@yme
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ulfametho!a@ole( asulfonamide that is astructural analog of*A3A( competitivelyinhibits the synthesisof dihydrofolic acidfrom *A3A%
Trimethoprim( astructural analog ofa portion of dihydrofolicacid( competitivelyinhibits the synthesisof tetrahydrofolic acid%
*A3A
ulfametho!a@ole
Dihydrofolic acid
Trimethoprim
Tetrahydrofolic acid
*A3A
ulfametho!a@ole
Dihydrofolic acid
Trimethoprim
*recursors of proteins(D4A( /4A
D4A/4A
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Chec 1our nderstanding+hat group of antibiotics interferes &ith the
$ -replicating en/y#e $ gyrase 20-11
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Commonly sed Antimicrobial Drugs
20-13 E!plain the #odes of action of currently usedantifungal drugs.
20-1 E!plain the #odes of action of currently usedanti(iral drugs.
20-1 E!plain the #odes of action of currently usedantiproto/oan and antihel#inthic drugs.
Learning Objectives
Antifungal Drugs?
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Antifungal Drugs? rgosterol ynthesis
*olyenes #photericin test +for epsilometer,( a gradient diffusion method that determines antibioticsensitivity and estimates minimal inhibitory concentration +:
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:
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Do!ycycline+9ro5th in all 5ells( resistant,
ulfametho!a@ole+Trailing end pointF usually read 5here thereis an estimated -0G reduction in gro5th,
treptomycin+4o gro5th in any 5ellF sensitive at allconcentrations,
>thambutol
+9ro5th in fourth 5ellsFe ually sensitive toethambutol and anamycin,
anamycin
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Chec 1our nderstanding
In the dis'-diffusion 94irby-
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/esistance to Antimicrobial Drugs
20-16 escribe the #echanis#s of drug resistance.
Learning Objective
"igure 20%2# The development of an antibiotic'resistant mutant during antibiotic therapy%
A ibi i i f b i l
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Days
3 a c
t e r i a
+ n u m
b e r
I m l ,
A n t i b i o t i c r e s i s t a n c e
+ m g
I m l ,
3acteriacount
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(ariety of #utations can lead to antibioticresistance
esistance genes are often on plas#ids ortransposons that can be transferred bet&een
bacteria
Antibiotic /esistance
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isuse of antibiotics selects for resistance #utantsisuse includes%
Gsing outdated or &ea'ened antibioticsGsing antibiotics for the co##on cold and other
inappropriate conditionsGsing antibiotics in ani#al feed"ailing to co#plete the prescribed regi#enGsing so#eone else s lefto(er prescription
$I *I $ ntibiotic esistance% "or#s of esistance
$I *I $ ntibiotic esistance% rigins of esistance
"igure 20%20 3acterial /esistance to Antibiotics%
http://antibiotic_origins.html/http://antibiotic_forms.html/7/26/2019 Ch 20: Antimirobial Drugs
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#% 3loc ing entry
2% fflu! of antibiotic
Antibiotic
Antibiotic
Antibiotic
n@ymatic action
Clinical "ocus Antibiotics in Animal "eed Lin ed to Human Disease( "igure A%
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/esistanceplasmid
E .
c o l i
S .
e n t e r i c a
S . e
n t e r i c a
a f t e r c o n
j u g a t
i o n
Cephalosporin'resistance in E.coli transferred by conjugation
to Salmonella enterica in theintestinal tracts of tur eys%
Clinical "ocus Antibiotics in Animal "eed Lin ed to Human Disease( "igure 3%
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"E forhumans
"E forpoultry
"E for poultrydiscontinued
#$- #$-- #$$0 #$$2 #$$. #$$ #$$- 2000 2002 200. 200 200-
1ear
* e r c e n
t " E ' r e s
i s t a n t C a m p y l o
b a c t e r
0
&
#0
#&
20
2&
60"louro uinolone'resistant Campylobacter jejuni in the nited tates( #$- )200-%
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Chec 1our nderstanding
+hat is the #ost co##on #echanis# that abacteriu# uses to resist the effects of penicillin20-16
>ffects of Combinations of Drugs
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g
20-18 Co#pare and contrast synergis# andantagonis#.
Learning Objective
>ffects of Combinations of Drugs
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g
ynergism occurs &hen the effect of t&o drugstogether is greater than the effect of either aloneAntagonism occurs &hen the effect of t&odrugs together is less than the effect of either
alone
"igure 20%26 An e!ample of synergism bet5een t5o different antibiotics%
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Dis 5ith antibioticamo!icillin'clavulanicacid
Dis 5ith antibiotica@treonam
Area of synergisticinhibition( clear
Area of gro5th(cloudy
Antibiotic afety
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y
*herapeutic inde!% ris' (ersus benefit
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Chec 1our nderstanding
*etracycline so#eti#es interferes &ith the acti(ityof penicillin. )o& 20-18
"uture of Chemotherapeutic Agents
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p g
20-1; Identify three areas of research on ne&che#otherapeutic agents.
Learning Objective
"uture of Chemotherapeutic Agents
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Antimicrobial peptides
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Cytoplasm
D4A
/4Atranscript
m/4A
An abnormal gene(cancer gene( or virusgene is transcribed in ahost cell%
si/4A bindsm/4A%
/< C brea sdo5n the /4Acomple!%
4o proteine!pression occurs%
si/4A
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Chec 1our nderstanding
+hat are defensins 20-1;