Chapter 3

Drug Resistance
Section 1

Drug resistance of
bacteria
 Antibacterial agents

Mechanism
1. Inhibition of cell wall synthesis
penicillins, cephalosporins ,vancomycin ……
sefəloʊs'pɔ:rɪnz 头孢菌素类 万古霉素

2. Alteration of cell membrane function

polymyxin, amphotericin B……
ˌpɒli:'mɪksɪn 多粘菌素 ˌæmfə'terəsɪn 两性霉素

3. Inhibition of protein synthesis

chloramphenicol, erythromycin, tetracyclines ……
ˌklɔ:ræm'fenɪkɒl 氯霉素 ɪˌrɪθrə'maɪsɪn 红霉素 tetrəsɪk'laɪnz 四环素

4. Inhibition of nucleic acid synthesis

sulfonamides, rifampin, quinolones……
sʌl'fɒnəmaɪdz 磺胺类药 rɪ'fæmpɪn kwaɪnə'loʊnz 喹诺酮类
物
 Section 2
Mechanism of Drug Resistance
 1 、 Genetic mechanism
ɪnˈtrɪnsɪk
* Intrinsic resistance ：
Bacteria absence of the target for the action of th
e drug or presence of a permeability barrier (pass
pɚmiəˈbɪlɪti
through)

* Acquired resistance ：
Chromosome mediated resistance
Plasmid mediated resistance
Transposon mediated resistance
Chromosome mediated resistance

Chromosomal resistance : due to a mutation in the gene th

at codes for the target of the drug, or for the transport system

in the membrane that controls the uptake of the drug.

 Plasmid mediated resistance

R plasmid RT
(RTF:resistance F
n 10
T
transfer factor)
'kɔndʒuɡeitiv
–Conjugative plasmid Tn
8
9
–Transfer genes Tn

R determinant Resistance ge R determinant

nes Transposons

Multiple resistan
Transposon mediated resistance

IS Resistance Gene(s) IS
Tn
 2 、 biochemica mechanism

Bacteria produce enzymes that in

activate the drugs

β-lactamase→cleaving the β-lactam ring of drug

'læktəmeɪs
→ inactivate penicillin,
cephalosporins
sefələʊs'pɔ:rɪnz 头孢菌素类
Bacteria develop an altered structural
target for the antibacterial drug

30S ribosomal subuint →mutant protein→

resisitance to streptomycin
ˌstreptə'maɪsɪn

23S rRNA →methylated → resisitance to

erythromycin
'meθɪleɪtɪd
ɪˌrɪθrə'maɪsɪn
 Bacteria decrease their permeability
and efflux pump system
'eflʌks

change portein →reduce the amount of drug

entering the bacterium. penicillin

multidrug resistance pump → exports a variety of fo

reign molecules including certain antibiotics, eg quinol
ones
Controlling Strategy against
Drug Resistance
1. correct usage of antibiotics
drug dosages and delivery routes
'dəʊsɪdʒɪz
Selection of drugs
Monitoring for resistance and early treatment
'mɒnɪtərɪŋ
2. Strict implementation of disinfection
 and isolationsystem
3. To strengthen the clear policy of using antibiotics

4. Study on the elimination of /get rid of the plasmid.

5. Studies of new antibiotics

药物轮换策略评价
6. Evaluation of drug rotation strategies