医学微生物学英文版教学课件：第4章 Bacterial Drug Resistance

1、Chapter 4Bacterial Drug Resistance Section 1Drug resistance of bacteriaAntibacterial agentsMechanism1. Inhibition of cell wall synthesis penicillins, cephalosporins ,vancomycin 2. Alteration of cell membrane function polymyxin, amphotericin B3. Inhibition of protein synthesis chloramphenicol, erythr

2、omycin, tetracyclines 4. Inhibition of nucleic acid synthesis sulfonamides, rifampin, quinolones超级细菌的历史 1920年，医院感染的主要病原菌是链球菌。 1960年，产生了耐甲氧西林的金黄色葡萄球菌（MRSA），MRSA取代链球菌成为医院感染的主要菌种。耐青霉素的肺炎链球菌同时出现。 1990年，耐万古霉素的肠球菌、耐链霉素的“食肉链球菌”被发现。 2000年，出现绿脓杆菌，对氨苄西林、阿莫西林、西力欣等8种抗生素的耐药性达100%；肺炎克雷伯氏菌，对西力欣、复达欣等16种高档抗生素的耐药性高达5

3、2%-100%。 2010年,研究者发现携有一个特殊基因的数种细菌具有超级抗药性，可使细菌获得超级抗药性的基因名为NDM1。 Section 2The Mechanism of Drug Resistance Hereditary mechanism of Drug Resistance Classification of Drug Resistance intrinsic resistance： naturally insensitive to a particular drug * absence of the target * presence of a permeability bar

4、rier acquired resistance： *Chromosome mediated resistance *Plasmid mediated resistance *Transposon mediated resistance Single drug resistanceChromosome mediated resistance Chromosomal resistance is due to a mutation in the gene that codes for either the target of the drug or the transport system in

5、the membrane that controls the uptake of the drug. R plasmid Tn 9Tn 21Tn 10Tn 8RTFR determinantRTFConjugative plasmidTransfer genesR determinantResistance genesTransposonsPlasmid mediated resistanceMultiple resistanceIS ISResistance Gene(s)Transposon mediated resistanceTnBiochemical Mechanism of Dru

6、g Resistance1.Bacteria produce enzymes that inactivate the drugs -lactamasecleaving the -lactam ring of drug inactivate penicillin, cephalosporins 2. Bacteria develop an altered structural target for the antibacterial drug 30S ribosomal subuint mutant protein resisitance to streptomycin 23S rRNA met

7、hylated resisitance to erythromycin Penicillin-binding protein loss/altered resisitance to penicillins, cephalosporins3.Bacteria decrease their permeability and efflux pump system change porin reduce the amount of drug entering the bacterium. penicillin multidrug resistance pump exports a variety of foreign molecules including certain antibiotics quinolones Controlling Strategy against Drug Resistance1. correct usage of antibiotics drug dosages and delivery routes Selection of drugs Monitoring for resistance and early treatment 2. Disinfection and isolation 3. Cle