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1、Chapter 4 Bacterial Heredity and Variation: Bacterial GeneticsXiao-Kui GUO Shanghai Jiao Tong University School of MedicineBacterial Genetics is the study of bacterial heredity and variation.Concept: Heredity: The “likeness”( similarity) of characteristics between progeny and parent. Variation: The

2、difference between progeny and parent. Phenotypic Variation: genetic& environmental changes Genotypic Mutation: Gene(s) mutation.Target of variationshape and structure variation: L formVirulence variation: BCG vaccine strain. Resistance variation: antibiotics Colony variation: Smooth rough 30g/L NaC

3、lYersinia pestis polymorphism old culture mediumBacterial Genome The molecular basis of genetic variationGenetic material of bacteria: DNABacterial genomeChromosomeExtrachromosomal genetic elementsPlasmidsProphageChromosome One long, double-stranded circular or linear single DNA moleculeContaining f

4、rom 580 kb to more than 4600 kb of DNA Genome organizationSpeciesDNA moleculesSize (Mb)Number of genesEscherichia coli K-12One circular molecule4.6394397Vibrio cholerae El Tor N16961Two circular moleculesChromosome12.9612770Chromosome21.0731115Deinococcus radiodurans R1Four circular moleculesChromos

5、ome 12.6492633Chromosome 20.412369Megaplasmid0.177145Plasmid0.04640Borrelia burgdorferi B31seven or eight circular molecules, 11 linear moleculesLinear chromosome0.911853Circular plasmid cp90.00912Circular plasmid cp260.02629Circular plasmid cp32*0.032Not knownLinear plasmid lp170.01725Linear plasmi

6、d lp250.02432Linear plasmid lp28-10.02732Linear plasmid lp28-20.03034Linear plasmid lp28-30.02941Linear plasmid lp28-40.02743Linear plasmid lp360.03754Linear plasmid lp380.03952Linear plasmid lp540.05476Linear plasmid lp560.056Not knownThere are 5 or 6 similar versions of plasmid cp32 per bacterium.

7、PlasmidsExtrachromosomal genetic elements; circular, double-stranded DNA moleculesAutonomously replicate, independent of the bacterial chromosomeCarry genetic information, which may not be essential but can provide a selective advantage to the bacteriaTransferable plasmidschromosomal DNA Bacteriocin

8、s Toxins Metabolism of some substratesFertility plasmid Plasmid-mediated antibiotic resistanceFunction of plasmidBacteriophageBacteriophages ( phages ) are obligate intracellular parasites that multiply inside bacteria using some or all of the host biosynthetic machinery. They are viruses that infec

9、t bacteria.Structure of Bacteriophage Types of BacteriophageLytic or Virulent Phages Lysogenic or Temperate Phage Lytic or Virulent PhagesDefinition: Lytic or virulent phages are phages which rapidly multiply in bacteria and kill the cell by lysis at the end of the life cycle.Life CycleAdsorptionPen

10、etration Biological SynthesisMaturation and Release Lytic phage are enumerated by a plaque assay. A plaque is a clear area which results from the lysis of bacteria. Each plaque arises from a single infectious phage. The infectious particle that gives rise to a plaque is called a pfu (plaque forming

11、unit). Lysogenic or Temperate PhageLysogenic or temperate phages are those that can either multiply via the lytic cycle or remain in a quiescent state in the cell. In this quiescent state most of the phage genes are not transcribed; the phage genome exists in a repressed state. The phage DNA in this

12、 repressed state is called a prophage because it is not a phage but it has the potential to produce phage. In most cases the phage DNA is inserted and integrated into the host chromosome and is replicated along with the host chromosome and passed on to the daughter cells. The cell harboring a propha

13、ge is termed a lysogenic bacterium. When a cell es lysogenized, occasionally exogenous genes carried by the phage get expressed in the bacteria, which can change properties of the host cell. This process is called lysogenic conversion. Lysogenic conversionC. diphtheriae phageC. diphtheriae toxin (-)

14、C. diphtheriae toxin (+)Transposable elementA mobile DNA sequence that can change its position within the genome or between different DNA molecules. Insertion sequences (IS) : The simplest transposons; carry no known genes except those that are required for transposition ( transposase)(2kb )Transpos

15、ons (Tn): transposable genetic elements that carry one or more other genes in addition to those that are essential for transposition. (2kb ) Mutator phageIS ISResistance Gene(s)TnSome pathogenic bacteria use a similar mechanism to coordinate the expression of a system of virulence factors. The genes

16、 for the activity may be grouped together in a pathogenicity or virulence island, which is surrounded by transposon-like mobile elements allowing them to move within the chromosome and to other bacteria. (EHEC,EPEC)locus for enterocyte effacement (LEE)Pathogenicity or virulence islandMechanism of ba

17、cterial variationGene mutationGene transfer and bination TransformationConjugation TransductionGene MutationMutation is caused by errors in the process of DNA replication that results in a change in the nucleotide sequence of genome of an organism. Gene transfer and bination Bacterial genetic exchan

18、ge is typified by transfer of a relatively small fragment of a donor genome to a recipient cell. The transferred donor DNA may then be integrated into the recipients nucleoid ( bination) by various mechanisms. Successful genetic bination demands that this donor DNA be replicated in the binant organi

19、sm. Natural mechanisms of gene transfer and bination in bacteria include TransformationConjugationTransductionTransformationThe process by which bacteria take up fragments of naked DNA and incorporate them into their genome. Transformation (Frederick Griffith, 1928) ConjugationFirst described by Led

20、erburg & Tatum in 1946 in a strain of E. coli called K12.A donor or male bacterium passes DNA directly to a recipient or female bacterium by a conjugation tube (sex pili). The female bacterium attains donor status & in turn can conjugate with other female cells.Maleness is determined by the presence

21、 of a plasmid which codes for sex pili.The plasmid is called sex factor or fertility factor (F factor)R (resistance) factor can also be transferred by conjugationF-Pilus for ConjugationF-pilus:encoded by the plasmid of “fertility factor (F factor)”F+ conjugationResistance plasmid conjugation Hfr ConjugationWhen it exists as a free plasmid, the F plasmid can only transfer itself. This isnt all that useful for genetics.However, sometimes th

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