1887

Chapter 3 : AraC Family Regulators and Transcriptional Control of Bacterial Virulence Determinants

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

AraC Family Regulators and Transcriptional Control of Bacterial Virulence Determinants, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817893/9781555812454_Chap03-1.gif /docserver/preview/fulltext/10.1128/9781555817893/9781555812454_Chap03-2.gif

Abstract:

This chapter focuses on selected members of the AraC/XylS family of regulatory proteins as a potential model system to study the induction of genes related to bacterial virulence in human infections. The structural analysis of an AraC family member, Rob, demonstrated some similarities to MarA but also some significant differences, suggesting that alternative modes of DNA binding may influence transcriptional activation relative to different promoter contexts. The activation of the AraC family regulators by their cognate ligand becomes an interesting variable when considering the number of AraC family proteins likely to be involved in the induction of virulence-related genes. The modulation of DNA binding by small molecules specific for AraC family members is a key issue when considering whether disruption of the activation process could be a useful therapeutic strategy. Arabinose binding frees the arms from their interaction with the DNA-binding domain, allowing a preferential interaction with the dimerization domain. Infections with bacteria producing urease often result in cystitis and acute pyelonephritis and can progress to bacteremia. Structural analysis of the AraC proteins has been slowed because of the general aggregation properties of these proteins, but new information is accumulating through the recognition of different functional domains, the construction of chimeric proteins, and the use of genetic approaches. The AraC family includes many transcriptional activators that enhance the production of bacterial virulence determinants.

Citation: Frank D, Hunt M. 2003. AraC Family Regulators and Transcriptional Control of Bacterial Virulence Determinants, p 39-54. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch3

Key Concept Ranking

Type III Secretion System
0.43494487
0.43494487
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

Structures of Rob and MarA in complex with target DNA sequences. The structurally similar N-terminal DNA binding domains are colored orange in the ribbon diagrams. The C-terminal domain unique to Rob is blue. MicF and MarA sequences used for cocrystallization are shown with Abox sequences in orange and B-box sequences in light blue type. Only the Nterminal HTH motif of Rob directly contacts bases of the binding sequence. MarA bends the DNA target so that both HTH motifs are located in adjacent major groove surfaces on one side of the DNA. From reference 8 with permission. (See Color Plates following p. 256.)

Citation: Frank D, Hunt M. 2003. AraC Family Regulators and Transcriptional Control of Bacterial Virulence Determinants, p 39-54. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch3
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Regulatory region of the operon, the binding sites for AraC (I, I, O, and O), and promoters and . The domains of AraC consisting of the N-terminal arm, the dimerization domain, the linker domain, and the DNAbinding domain are marked. The light switch mechanism is illustrated. In the absence of arabinose the N-terminal arms interact with the DNAbinding domain and cause the protein to assume an extended conformation and preferential binding to distal I and O sites, forming a DNA loop and repressing transcription from and . Arabinose-binding changes the orientation of the arms and allows binding to adjacent I and I sites. AraC bound to the O site in the presence of arabinose is shown in gray to illustrate partial occupancy. From reference with permission.

Citation: Frank D, Hunt M. 2003. AraC Family Regulators and Transcriptional Control of Bacterial Virulence Determinants, p 39-54. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch3
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

The operons of type III secretion system and effector toxins ExoU, ExoS, ExoT, and ExoY are shown. Individual gene products are indicated as colored arrows (the sizes of protein products are approximate and not to scale). Different colors are used to identify operons based on promoter mapping, transcriptional fusion, or DNA-binding analyses. The toxins and known chaperone proteins are located in different chromosomal locations than the set of operons that encode the secretory, translocation, and regulatory proteins. ExsA consensus and imperfect binding sites are illustrated. (See Color Plates following p. 256.)

Citation: Frank D, Hunt M. 2003. AraC Family Regulators and Transcriptional Control of Bacterial Virulence Determinants, p 39-54. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch3
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Location and orientation of the consensus binding sites for members of the AraC protein family: (A) ExsA, (B) UreR, and (C) Rns. Open reading frames are represented by open arrows. Bent arrows illustrate experimentally defined transcriptional start sites, and filled boxes indicate the sigma-70 promoter hexamers. A striped bar indicates a putative promoter region identified by sequence homology. An asterisk located within the operon is used to identify a UreR + urea-dependent start site present only in the plasmid-encoded locus. Positions of the Rns-binding sites 1, 2, and 3 and sites I and II are numbered relative to the transcriptional start sites. The two binding sites within are numbered relative to the translational start codon. Putative Rns-binding sites that overlap with the -35 hexamer or are within the coding region are marked with a # sign. Information used to assemble this summary figure was derived from references , and . Figure is not to scale.

Citation: Frank D, Hunt M. 2003. AraC Family Regulators and Transcriptional Control of Bacterial Virulence Determinants, p 39-54. In Burns D, Barbieri J, Iglewski B, Rappuoli R (ed), Bacterial Protein Toxins. ASM Press, Washington, DC. doi: 10.1128/9781555817893.ch3
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555817893.chap3
1. D’Orazio, S. E. F.,, and C. M. Collins. 1995. UreR activates transcription at multiple promoters within the plasmid-encoded urease locus of the Enterobacteriaceae. Mol. Microbiol. 16:145155.
2. D’Orazio, S. E. F.,, V. Thomas,, and C. M. Collins. 1996. Activation of transcription at divergent urea-dependent promoters by the urease gene regulator UreR. Mol. Microbiol. 21:643655.
3. Frank, D. W. 1997. The exoenzyme S regulon of Pseudomonas aeruginosa. Mol. Microbiol. 26:621629.
4. Gallegos, M.-T.,, R. Schleif,, A. Bairoch,, K. Hofmann,, and J. L. Ramos. 1997. AraC/ XylS family of transcriptional regulators. Microbiol. Mol. Biol. Rev. 61:393410.
5. Goranson, J.,, A. K. Hovey,, and D. W. Frank. 1997. Functional analysis of exsC and exsB in the regulation of exoenzyme S production from Pseudomonas aeruginosa. J. Bacteriol. 179:16461654.
6. Harmer, T.,, M. Wu,, and R. Schleif. 2001. The role of rigidity in DNA loopingunlooping by AraC. Proc. Natl. Acad. Sci. USA 98:427431.
7. Hovey, A. K.,, and D. W. Frank. 1995. Analyses of the DNA-binding and transcriptional activation properties of ExsA, the transcriptional activator of the Pseudomonas aeruginosa exoenzyme S regulon. J. Bacteriol. 177:44274436.
8. Kwon, H. J.,, M. H. J. Bennik,, B. Demple,, and T. Ellenberger. 2000. Crystal structure of the Escherichia coli Rob transcription factor in complex with DNA. Nat. Struct. Biol. 7:424430.
9. Martin, R. G.,, and J. L. Rosner. 2001. The AraC transcriptional activators. Curr. Opin. Microbiol. 4:132137.
10. Munson, G. P.,, L. G. Holcomb,, and J. R. Scott. 2001. Novel group of virulence activators within the AraC family that are not restricted to upstream binding sites. Infect. Immun. 69:186193.
11. Munson, G. P.,, and J. R. Scott. 1999. Binding site recognition by Rns, a virulence regulator in the AraC family. J. Bacteriol. 181:21102117.
12. Munson, G. P.,, and J. R. Scott. 2000. Rns, a virulence regulator within the AraC family, requires binding sites upstream and downstream of its own promoter to function as an activator. Mol. Microbiol. 36:13911402.
13. Poore, C. A.,, C. Coker,, J. D. Dattelbaum,, and H. L. T. Mobley. 2001. Identification of the domains of UreR, an AraC-like transcriptional regulator of the urease cluster in Proteus mirabilis. J. Bacteriol. 183:45264535.
14. Rhee, S.,, R. G. Martin,, J. L. Rosner,, and D. R. Davies. 1998. A novel DNA-binding motif in MarA: the first structure for an AraC family transcriptional activator. Proc. Natl. Acad. Sci. USA 95:1041310418.
15. Soisson, S. M.,, B. MacDougall-Shackleton,, R. Schleif,, and C. Wolberger. 1997. Structural basis for ligand-regulated oligomerization of AraC. Science 276:421425.
16. Thomas, V. J.,, and C. M. Collins. 1999. Identification of UreR binding sites in the Enterobacteriaceae plasmid-encoded and Proteus mirabilis urease gene operons. Mol. Microbiol. 31:14171428.
17. Yahr, T.,, and D. W. Frank. 1994. Transcriptional organization of the trans-regulatory locus which controls exoenzyme S synthesis in Pseudomonas aeruginosa. J. Bacteriol. 176:38323838.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error