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Genetics: From Genes to Genomes

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1 Genetics: From Genes to Genomes
PowerPoint to accompany Genetics: From Genes to Genomes Fourth Edition Leland H. Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, and Lee M. Silver Prepared by Mary A. Bedell University of Georgia Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition

2 15 Gene Regulation in Prokaryotes CHAPTER OUTLINE PART V
How Genes Are Regulated CHAPTER Gene Regulation in Prokaryotes CHAPTER OUTLINE 15.1 Overview of Prokaryotic Gene Regulation 15.2 The Regulation of Gene Transcription 15.3 Attenuation of Gene Expression: Termination of Transcription 15.4 Global Regulatory Mechanisms 15.5 A Comprehensive Example: The Regulation of Virulence Genes in V. cholerae Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

3 RNA polymerase participates in all three phases of transcription
Initiation – core RNA polymerase plus sigma (σ) factor Core has four subunits: two alpha (α), one beta (β), one beta prime (β') DNA is unwound and polymerization begins Elongation – core RNA polymerase without σ factor Continues until RNA polymerase recognizes termination signal Termination – two kinds in bacteria Rho-dependent – Rho (ρ) protein binds to RNA polymerase and removes it from RNA Rho-independent – 20 nt sequence in RNA forms stem-loop Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

4 Role of RNA polymerase in initiation and elongation phases of transcription
Fig. 15.2 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

5 Two kinds of transcription termination in bacteria
Fig (cont) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

6 Regulation of expression can occur at many steps
Transcriptional control Binding of RNA polymerase to promoter Most critical step in regulation of most prokaryotic genes Shift from initiation to elongation Release of mRNA at termination Posttranscriptional control Stability of mRNA Efficiency of translation initiation Stability of polypeptide Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

7 Utilization of lactose by E
Utilization of lactose by E. coli provides a model system of gene regulation Lactose utilization requires two enzymes (Fig. 15.3) Permease transports lactose into cell β-Galactosidase (β-Gal) splits lactose into glucose and galactose In the absence of lactose, both enzymes are present at very low levels Lactose is the inducer of the genes encoding permease and β-Gal Induction – stimulation of synthesis of a specific protein Inducer – molecule responsible for induction Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

8 Lactose utilization in an E. coli cell
Fig. 15.3 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

9 Advantages of using lactose utilization by E
Advantages of using lactose utilization by E. coli as a model for understanding gene regulation Lac− mutants can be maintained on media with glucose and so lac genes are not essential for survival If both glucose and lactose are present, E. coli cells will use glucose first Simple assays for lac expression - use of ONPG or X-gal as substrates for β-gal (color change) Lactose induces a 1000-fold increase in β-gal activity Detection and characterization of hundreds of lac− mutants defective in lactose utilization Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

10 Studies of lac− mutants revealed the operon theory of gene regulation
Jacques Monod and Francois Jacob – Pasteur Institute Nobel Prize in 1965 (with A. Lwoff) for their discoveries concerning genetic control of enzyme and virus synthesis Compared the effects of many different types of lac mutants on induction and repression of enzyme activity for lactose utilization Operon theory - one signal can simultaneously regulate expression of several clustered genes Hypothesized that lac genes are transcribed together as a single mRNA (polycistronic) from a single promoter Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

11 The lactose operon in E. coli
The players Three structural genes - lacZ, lacY, and lacA Promoter - site to which RNA polymerase binds Cis-acting operator site – controls transcription initiation Trans-acting repressor - binds to the operator (encoded by lacI gene) Inducer - prevents repressor from binding to operator Fig. 15.5a Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

12 Repression of lac gene expression
In the absence of lactose, repressor binds to the operator and prevents transcription lac repressor is a negative regulatory element Fig. 15.2b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

13 Induction of the lac operon in E. coli
When lactose (or IPTG) is present: Inducer binds to the lac repressor Repressor changes shape and cannot bind to operator RNA polymerase binds to the promoter and initiates transcription of the polycistronic lac mRNA Fig. 15.2c Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

14 Jacob and Monod defined the roles of the lac genes by genetic analysis of many lacI− mutants
Complementation analysis identified three genes in a tightly linked cluster lacZ encodes β-galactosidase lacY encodes permease lacA encodes transacetylase Most studies focused on lacZ and lacY Constitutive expression of β-galactosidase and permease was caused by mutations in the lacI gene Constitutive mutants (lacI−) express the enzymes in the absence and presence of inducer Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

15 The PaJaMo experiment provided evidence that lacI encodes a repressor
lacI+ lacZ+ DNA transferred into lacI− lacZ− cells β-gal levels increased initially β-gal levels decreased as repressor accumulated β-gal accumulation resumed after addition of inducer Fig. 15.7 Jacob and Monod proposed that lacI encodes a repressor that binds to an operator site near the lac promoter Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

16 How the inducer acts to trigger synthesis of lac enzymes
Binding of inducer to repressor changes the shape of the repressor so that it can longer bind to DNA When no inducer is present, repressor is able to bind to DNA Repressor is an allosteric protein – undergoes reversible changes in conformation when bound to another molecule Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

17 lacl− mutants have a mutant repressor that cannot bind to operator
In lacI− mutants, lac genes are expressed in the absence and the presence of inducer (constitutive expression) Fig. 15.8 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

18 lacls mutants have a superrepressor that binds to operator but cannot bind to the inducer
In lacIS mutants, lac genes are repressed in the absence and the presence of inducer Fig. 15.9 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

19 lac repressor has two separate domains
Mutated sequences in many different lacI− mutants clustered in the DNA-binding domain Mutated sequences in many different lacIS mutants clustered in the inducer-binding domain X-ray crystallography revealed the two separate domains Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

20 lacOc mutants have a mutant operator that cannot bind the repressor
In lacOc mutants, lac genes are expressed in the absence and the presence of inducer (constitutive expression) Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

21 Proteins act in trans, DNA sites act in cis
Jacob and Monod used partial diploids carrying different alleles of lac regulatory elements and structural genes to identify trans-acting and cis-acting elements F' lac plasmids (Chapter 14) were used to generate partial diploids Trans-acting elements: Can diffuse through the cytoplasm and act at target DNA sites on any DNA molecule in the cell Cis-acting elements: Can only influence expression of adjacent genes on the same DNA molecule Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

22 Lacl+ protein acts in trans
Fig Repressor expressed from the plasmid can diffuse through the cytoplasm and bind to the operator on the chromosome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

23 Lacls protein acts in trans
Fig Superrepressor expressed from the plasmid can diffuse through the cytoplasm and bind to the operator on the chromosome, even in the presence of inducer Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

24 lacOc acts in cis Fig The lacOC mutation affects expression of genes only on the DNA that it is located on Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

25 The lac operon of E. coli is regulated by both lactose and glucose
When both glucose and lactose are present, only glucose is utilized Lactose induces lac mRNA expression, but only in the absence of glucose Lactose prevents repressor from binding to lacO lac repressor is a negative regulator of lac transcription lac mRNA expression cannot be induced if glucose is present Glucose controls the levels of cAMP cAMP binds to cAMP receptor protein (CRP) CRP-cAMP is a positive regulator of lac transcription Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

26 Positive regulation by CRP–cAMP
Catabolite repression – overall effect of glucose is to prevent lac gene expression Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

27 Positive regulation of the araBAD operon by AraC
Three structural genes required in the breakdown of the sugar arabinose - araB, araA, and araD Arabinose genes are in an operon and are induced when arabinose is present AraC is a positive regulator of the araBAD operon Loss of function of AraC results in no expression of the araBAD operon when arabinose was present Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

28 AraC is a positive regulator
Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

29 Further studies revealed more about regulatory proteins and sites
Biochemical evidence for lac repressor binding to lacO (Fig ) X-ray crystallography revealed the structure of repressor proteins lac repressor has a helix-turn-helix (HTH) motif (Fig ) Evidence that specific amino acids in the α-helices of lac repressor are required for binding to lacO (Fig ) DNA sequences to which negative and positive regulators bind have a two-fold rotational symmetry e.g. CRP-binding site of the lac operon Most DNA-binding regulatory proteins are oligomeric, with two to four subunits Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

30 The lac repressor binds to operator DNA
Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

31 DNA recognition sequences by helix-turn-helix (HTH) motif
A protein with an HTH motif has two α-helical regions separated by a turn in the protein The HTH motif fits into the major groove of DNA One of the α-helices recognizes a specific DNA sequence Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

32 Changing amino acids in recognition sequence of a repressor protein
434 repressor binds to an operator in the DNA of the 434 virus P22 repressor binds to an operator in the DNA of the P22 virus Amino acid sequences in the α-helix of 434 repressor were modified to have amino acid sequence like that of P22 repressor Hybrid 434-P22 functioned just like the P22 repressor Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

33 DNase footprint shows where proteins bind
Incubate radiolabeled DNA from lac+ operon with partially purified protein from lacI+ cells Partial digest of DNA with DNase I Gel electrophoresis and autoradiography If protein is bound to DNA, then specific fragments will be protected from DNase I digestion Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

34 CRP–cAMP binds as a dimer to a regulatory region
CRP-binding sites have a two-fold rotational symmetry CRP protein binds as a dimer CRP-binding site consists of two recognition sequences, one for each subunit of the CRP dimer 5'TGTGAGTTAGCTCACA 3' 3'ACACTCAATCGAGTGT 5' Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

35 lac repressor tetramer binds to two sites
lac repressor is a tetramer, with each subunit containing a DNA-binding HTH motif lac operon has three operators (O1, O2, and O3) each of which contains two recognition sequences for lac repressor O1 has the strongest binding affinity for lac repressor Maximal repression occurs when all four repressor subunits are bound Two repressor subunits bind to O1 Two repressor subunits bind to either O2 or O3 Fig. 15.2 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

36 AraC acts as both a repressor and an activator
AraC can bind to three sites (araO, araI1, and araI2) with different affinities (a) No arabinose present: When AraC is bound to araO and to araI1, looping of DNA occurs and prevents transcription (b) Arabinose present: Arabinose causes allosteric change in AraC so that it cannot bind to araO AraC interacts with RNA polymerase only when both araI1 and araI2 are occupied Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

37 Interaction of regulatory proteins with RNA polymerase
Many negative regulators (e.g. lac repressor) prevent transcription initiation by blocking the functional binding of RNA polymerase (Fig ) Many positive regulators (e.g. CRP-cAMP) establish contact with RNA polymerase that enhances transcription initiation (Fig ) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

38 Overlapping binding sites for RNA polymerase and lac repressor
When lac repressor is bound to lac operator, functional binding of RNA polymerase to the promoter is blocked Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

39 CRP-cAMP complex makes direct contact with RNA polymerase
Without interaction with CRP-cAMP, RNA polymerase can bind to the promoter but is less likely to unwind DNA and initiate transcription Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

40 Using the lacZ gene as a reporter of gene expression
Reporter gene – protein-encoding gene whose expression in the cell is quantifiable by sensitive and reliable techniques Measuring gene expression Fuse coding region of lacZ to cis-acting regulatory regions from other genes (Fig ) Identifying sets of genes regulated by the same stimulus Create library of cells with promoter-less lacZ inserted by transposition into random sites in the genome (Fig ) Controlling gene expression Fuse the lac regulatory sequences to the coding region of a foreign gene (Fig ) Inducible expression of the foreign gene controlled by IPTG Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

41 lacZ fusion used to perform genetic studies of the regulatory region of gene X
Conditions that regulate expression of the test regions from gene X will alter the levels of β-galactosidase Specific regulatory sites can be identified by constructing and testing mutations in the test regions of gene X Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

42 Using lacZ to identify sets of genes regulated by the same stimulus
Fig Transposition of promoter-less lacZ coding region Library of clones containing lacZ insertions at random sites Screen library to identify all the genes that express lacZ in response to a signal Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

43 Use of fusions to overproduce a gene product
Expression of gene X under control of the lac regulatory system Fig a Expression of human growth hormone in E. coli controlled by lac control region Fig b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

44 Regulation of the tryptophan (trp) operon in E. coli
Structural genes for tryptophan (Trp) biosynthesis are expressed only in the absence of Trp Two mechanisms for trp operon regulation TrpR gene encodes the trp repressor that can bind to the Trp operator (TrpO) When Trp is present, TrpR repressor binds to TrpO When Trp is absent, TrpR repressor cannot bind to TrpO Attenuation controls termination of transcription in the trp leader (TrpL) When Trp is present, transcription terminates in TrpL When Trp is absent, transcription doesn't terminate in TrpL Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

45 Tryptophan acts as a corepressor
Binding of tryptophan to TrpR repressor allows TrpR to bind to TrpO and inhibit transcription of the five structural genes In the absence of tryptophan, TrpR repressor cannot bind to TrpO Fig a Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

46 Evidence that TrpR repressor is not the only regulator of the trp operon
Constitutive expression of Trp biosynthesis doesn't occur in TrpR− mutants If TrpR were the sole regulator, maximal expression of trp genes would occur in the absence or presence of tryptophan Second regulatory mechanism is attenuation – control of gene expression by premature termination of transcription Table15.1 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

47 Transcription from the trp promoter produces two alternative mRNAs
Attenuation controls termination of transcription in the trp leader (TrpL) Truncated mRNA - terminates in TrpL, only 140 bases Full-length mRNA - continues through TrpL and encodes all five structural genes Fig b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

48 Alternate stem-loop structures in trpL RNA
Different regions of trpL have complementary base-pairing Formation of the 1-2 stem-loop allows formation of the stem-loop Formation of the 2-3 stem-loop prevents formation of the 3-4 stem-loop The 3-4 stem loop is a transcription terminator Fig a Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

49 When tryptophan is present, transcription terminates in trpL because of translation
The trpL mRNA is translated and includes two trp codons Movement of ribosomes through trpL mRNA depends on the availability of tRNATrp When Trp is present, tRNATrp is available and rapid ribosome movement allows the formation of 3-4 stem-loop Fig b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

50 When tryptophan isn't present, transcription doesn't terminate in trpL
Fig c Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

51 Global regulatory mechanisms
Dramatic shifts in environmental conditions can trigger expression of sets of genes or operons Regulon – a group of genes whose expression is controlled by the same regulatory protein Two examples in E. coli: CRP-cAMP controls several catabolic operons Expression of several genes induced by heat shock Highly conserved stress response Induced proteins include those that recognize and degrade aberrant proteins and chaperones, which assist in preventing protein aggregation Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

52 Sigma factor (σ) recognition sequences
Normal, housekeeping sigma factor is σ70 Active under normal physiological conditions, but is inactivated by heat shock rpoH genes encodes σ32, an alternative sigma factor Heat shock inducible genes have promoters that are recognized by σ32 σ32 is resistant to inactivation by heat shock Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

53 Factors influencing increase in σ32 activity after heat-shock treatment
Increased transcription of rpoH gene Increased translation of σ32 mRNA because of increased stability of rpoH mRNA Increased stability and activity of σ32 protein No longer inhibited by chaperones DnaJ/K No competition from σ70 because it is removed by degradation Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

54 Alternate sigma factor in the heat-shock response
At normal temperatures, promoter for rpoH gene is recognized by σ70 After heat shock, σ70 is degraded and transcription of the gene for σ24 is increased σ24 recognizes a different promoter sequence at rpoH Increased expression of σ32 causes transcription of several genes Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

55 Translational control of another sigma factor encoded by the rpoS gene
Under normal conditions, rpoS gene is transcribed but rpoS mRNA is not translated After stress response, a small RNA (dsrA) binds to rpoS mRNA and allows translation Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

56 Tools for studying genes regulated in a global response
Microarrays of expression in different growth conditions, e.g. E. coli grown on glucose, glycerol, succinate, or alanine Switch from glucose to glycerol or succinate caused increased expression of 40 genes Switch from glucose to alanine caused increased expression of 188 genes Mutants in specific genes, e.g. NtrC is a master control gene activated by lack of ammonia Computer analysis to identify regulatory proteins, e.g. searches for HTH DNA binding motif Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

57 A comprehensive example: The regulation of virulence genes in V
A comprehensive example: The regulation of virulence genes in V. cholerae V. cholerae is the bacterial species that causes cholera, a life-threatening diarrheal disease Bacteria are ingested in contaminated drinking water Respond to changes in environment by increasing or decreasing transcription and/or translation of specific genes In intestine, V. cholerae express proteins to make flagella and to degrade mucous so that they can reach epithelial cells Once the bacteria reach the epithelial cells, they secrete toxins that result in diarrhea Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

58 Identification of regulators of toxin production in V. cholerae
Two genes, ctxA and ctxB, identified that encode subunits of cholera toxin Gene fusions of ctxA promoter and lacZ coding region created and transformed into E. coli Transformation of E. coli with ctxA-lacZ reporter gene with fragments of V. cholerae genomic DNA toxR gene from V. cholerae identified in genomic DNA that caused increased expression of ctxA-lacZ reporter gene Further experiments showed that mutation of toxR gene in V. cholerae abolished its virulence Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

59 Identification of other V. cholerae genes regulated by toxR
Library of V. cholerae cells created that had random insertions of lacZ coding region Gene fusions of a constitutive promoter and toxR coding region created and transformed into the lacZ library Colonies with high β-gal expression had lacZ sequences inserted adjacent to promoters regulated by toxR In E. coli, toxR could not affect expression of the same genes ToxT was then identified as a positive regulator of many V. cholera virulence genes TcpP and ToxR both bind to ToxT promoter and are both required for ToxT transcription Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

60 Model for how V. cholerae regulates genes for virulence
Fig Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15

61 Unanswered questions about expression of virulence genes in V. cholera
What is the signal that makes cholera bacteria stop swimming and start colonizing the intestinal epithelial cells? What molecular events differentiate swimming versus adherence? Why is there a cascade of regulatory factors (ToxR and ToxT)? A better understanding of V. cholerae pathogenesis will lead to more effective treatments and preventatives for cholera Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 15


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