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Chapter 18 : Role of Cyclic Di-GMP in Biofilm Development and Signaling in

Authors: Robert D. Perry1, Alexander G. Bobrov2
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Affiliations: 1: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536-0298; 2: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536-0298
Content Type: Monograph
Publication Year: 2010

Category: Microbial Genetics and Molecular Biology

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Role of Cyclic Di-GMP in Biofilm Development and Signaling in , Page 1 of 2

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Abstract:

, a gram-negative bacterium and member of the family, is the causative agent of bubonic, septicemic, and pneumonic plague. In general, increased levels of cyclic di-GMP (c-di-GMP) inside bacterial cells correlate with biofilm formation and expression of exopolysaccharide (EPS) and adherence factors, while decreased intracellular levels stimulate motility and a planktonic lifestyle. c-di-GMP homeostasis is carried out by GGDEF domain proteins, cyclic diguanylate cyclases (DGCs), which synthesize c-di-GMP, as well as EAL and HD-GYP domain proteins, c-di-GMP phosphodiesterases (PDEs), which degrade this nucleotide. was reported to express an Hms-dependent biofilm EPS, based on electron microscopy, reaction with antisera against poly-β-1,6-GlcNAc, and on the ability of cells to bind Congo red (CR), calcofluor white, and ruthenium red, each shown to stain various polysaccharides. A mutant overproduces biofilm but shows no increase in the levels of HmsHFRS proteins. All other potential DGCs and PDEs encoded by the KIM6+ genome do not compensate for or mutations, and the authors' analysis suggests that HmsT and Y3730 are the only two functional DGCs and that HmsP is the only functional PDE in . Mutations in (encoding ornithine decarboxylase), (encoding arginine decarboxylase), or both genes cause progressively lower intracellular levels of putrescine and a corresponding loss of crystal violet staining as a measure of adherence. Currently, only biofilm development is known to be controlled by c-di-GMP signaling in .

Citation: Perry R, Bobrov A. 2010. Role of Cyclic Di-GMP in Biofilm Development and Signaling in , p 270-281. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch18
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Role of Cyclic Di-GMP in Biofilm Development and Signaling in Yersinia pestis
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Citation: Perry R, Bobrov A. 2010. Role of Cyclic Di-GMP in Biofilm Development and Signaling in , p 270-281. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch18
/content/10.1128/9781555816667.ch18.ch18fig01
Figure 1.
Transmission routes of plague. For simplicity, some occasional transmission routes are not shown. Transmission via ingestion of infected rodents by wild or domesticated carnivores and subsequent interaction with humans is not shown. This figure was slightly modified from a figure kindly provided by Ken Gage, CDC.
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Image of Figure 1.
Figure 1.

Transmission routes of plague. For simplicity, some occasional transmission routes are not shown. Transmission via ingestion of infected rodents by wild or domesticated carnivores and subsequent interaction with humans is not shown. This figure was slightly modified from a figure kindly provided by Ken Gage, CDC.

Citation: Perry R, Bobrov A. 2010. Role of Cyclic Di-GMP in Biofilm Development and Signaling in , p 270-281. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch18
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Figure 2.
Proposed model for life cycle regulation of by c-di-GMP. We hypothesize that c-di-GMP reciprocally regulates biofilm and virulence factors in High levels of c-di-GMP mediated by the GGDEF domain protein HmsT have been proven to be required for biofilm formation in the flea. During growth in mammals, decreases in c-di-GMP in cells due to the EAL domain protein HmsP lead to a transition to a planktonic state. We hypothesize that decreased c-di-GMP levels may also enhance expression of mammalian virulence factors. The image of the blocked flea was reproduced from Fig. 1B from Hinnebusch et al. ( ) with permission of the American Association for the Advancement of Science.
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Image of Figure 2.
Figure 2.

Proposed model for life cycle regulation of by c-di-GMP. We hypothesize that c-di-GMP reciprocally regulates biofilm and virulence factors in High levels of c-di-GMP mediated by the GGDEF domain protein HmsT have been proven to be required for biofilm formation in the flea. During growth in mammals, decreases in c-di-GMP in cells due to the EAL domain protein HmsP lead to a transition to a planktonic state. We hypothesize that decreased c-di-GMP levels may also enhance expression of mammalian virulence factors. The image of the blocked flea was reproduced from Fig. 1B from Hinnebusch et al. ( ) with permission of the American Association for the Advancement of Science.

Citation: Perry R, Bobrov A. 2010. Role of Cyclic Di-GMP in Biofilm Development and Signaling in , p 270-281. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch18
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Figure 3.
Hms-dependent biofilm model of protein interactions and temperature regulation. Chains of circles represent linked monomers of the EPS component of the biofilm (different shades represent acetylated and deacetylated monomers). Predicted or hypothesized protein activities: HmsH, porin for polysaccharide export; HmsF, polysaccharide deacetylase; HmsR, glycosyl transferase; HmsS, assists HmsR in EPS synthesis. HmsT is a proven DGC (GGDEF domain), while HmsP is a proven c-di-GMP PDE (EAL domain). HmsP and HmsT form homodimers with HmsP interacting with HmsR and HmsT. HmsR also interacts with HmsS. HmsS is shown as a homodimer due to preliminary results that have not yet been confirmed. Cytoplasmic domains and periplasmic loops of IM proteins are shown as well as the putative lipoporotein linkage of HmsF and the periplasmic domain of HmsH. For simplicity, the defective GGDEF domain of HmsP is not shown. The plus sign indicates likely stimulation of HmsR enzymatic activity by c-di-GMP. At 26 to 34°C, Hms proteins are highly expressed (A), while at 37°C, the levels of Hms proteins are reduced to varying degrees (B). HmsT is degraded, thus reducing c-di-GMP levels. This, along with low levels of HmsR and HmsH, prevents significant biofilm formation. L-di-GMP, linear di-GMP; OM, outer membrane; GT, glycosyltransferase.
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Image of Figure 3.
Figure 3.

Hms-dependent biofilm model of protein interactions and temperature regulation. Chains of circles represent linked monomers of the EPS component of the biofilm (different shades represent acetylated and deacetylated monomers). Predicted or hypothesized protein activities: HmsH, porin for polysaccharide export; HmsF, polysaccharide deacetylase; HmsR, glycosyl transferase; HmsS, assists HmsR in EPS synthesis. HmsT is a proven DGC (GGDEF domain), while HmsP is a proven c-di-GMP PDE (EAL domain). HmsP and HmsT form homodimers with HmsP interacting with HmsR and HmsT. HmsR also interacts with HmsS. HmsS is shown as a homodimer due to preliminary results that have not yet been confirmed. Cytoplasmic domains and periplasmic loops of IM proteins are shown as well as the putative lipoporotein linkage of HmsF and the periplasmic domain of HmsH. For simplicity, the defective GGDEF domain of HmsP is not shown. The plus sign indicates likely stimulation of HmsR enzymatic activity by c-di-GMP. At 26 to 34°C, Hms proteins are highly expressed (A), while at 37°C, the levels of Hms proteins are reduced to varying degrees (B). HmsT is degraded, thus reducing c-di-GMP levels. This, along with low levels of HmsR and HmsH, prevents significant biofilm formation. L-di-GMP, linear di-GMP; OM, outer membrane; GT, glycosyltransferase.

Citation: Perry R, Bobrov A. 2010. Role of Cyclic Di-GMP in Biofilm Development and Signaling in , p 270-281. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch18
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Figure 4.
Dot blot analysis of poly-β-1,6-GlcNAc-like EPS production by strains. cells were grown at 26°C overnight in PMH2 with 0.05% D-glucosamine, and crude polysaccharide extracts were spotted onto a nitrocellulose membrane. Blots were developed with antisera against purified polysaccharide intercellular adhesion of ( ).
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Image of Figure 4.
Figure 4.

Dot blot analysis of poly-β-1,6-GlcNAc-like EPS production by strains. cells were grown at 26°C overnight in PMH2 with 0.05% D-glucosamine, and crude polysaccharide extracts were spotted onto a nitrocellulose membrane. Blots were developed with antisera against purified polysaccharide intercellular adhesion of ( ).

Citation: Perry R, Bobrov A. 2010. Role of Cyclic Di-GMP in Biofilm Development and Signaling in , p 270-281. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch18
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Figure 5.
Confocal laser scanning microscopy images of green fluorescent protein-expressing cells. Cultures were grown at 26°C overnight in PMH2 with 0.2% glucose in a conical tube with a coverslip. Cells attached to the glass coverslip (at the air-liquid interface) were visualized with a Leica TCS laser scanning confocal microscope. The xzy plane (a cross-sectional view) is shown. Hms and HmsH strains are positive and negative controls, respectively. The figure uses black and white unpublished images from the experiment depicted in Fig. 6 from Kirillina et al. ( ).
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Image of Figure 5.
Figure 5.

Confocal laser scanning microscopy images of green fluorescent protein-expressing cells. Cultures were grown at 26°C overnight in PMH2 with 0.2% glucose in a conical tube with a coverslip. Cells attached to the glass coverslip (at the air-liquid interface) were visualized with a Leica TCS laser scanning confocal microscope. The xzy plane (a cross-sectional view) is shown. Hms and HmsH strains are positive and negative controls, respectively. The figure uses black and white unpublished images from the experiment depicted in Fig. 6 from Kirillina et al. ( ).

Citation: Perry R, Bobrov A. 2010. Role of Cyclic Di-GMP in Biofilm Development and Signaling in , p 270-281. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch18
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Figure 6.
IM topology models of HmsP and HmsT. Dark grey boxes represent TM domains. Periplasmic and cytoplasmic domains are based on analysis of and fusions ( ). HAMP, EAL, and GGDEF domains are shown as light grey boxes. For HmsP, the GGDEF domain likely lacks DGC activity, since residues essential for this activity have been altered to SKTEF (shown in oval). E506 and D626 residues as well as the EAL motif within the EAL domain of HmsP are critical for PDE activity while the GGDEF residues of HmsT are essential for biofilm development ( ). Modified and reproduced from reference with permission of Blackwell Publishing.
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Image of Figure 6.
Figure 6.

IM topology models of HmsP and HmsT. Dark grey boxes represent TM domains. Periplasmic and cytoplasmic domains are based on analysis of and fusions ( ). HAMP, EAL, and GGDEF domains are shown as light grey boxes. For HmsP, the GGDEF domain likely lacks DGC activity, since residues essential for this activity have been altered to SKTEF (shown in oval). E506 and D626 residues as well as the EAL motif within the EAL domain of HmsP are critical for PDE activity while the GGDEF residues of HmsT are essential for biofilm development ( ). Modified and reproduced from reference with permission of Blackwell Publishing.

Citation: Perry R, Bobrov A. 2010. Role of Cyclic Di-GMP in Biofilm Development and Signaling in , p 270-281. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch18
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Figure 7.
Western blot analysis of HmsR and HmsS protein levels in strains after growth at 26°Cor 37°C. Equal concentrations of whole-cell lysates were separated by sodium dodecyl sul-fate-polyacrylamide gel electrophoresis; immunoblots were reacted with antiserum against the indicated Hms proteins. The negative control lane has a whole-cell lysate from a mutant that lacks 102 kb of chromosomal DNA that includes the operon. Modified and reproduced from Kirillina et al. ( ) with permission of Blackwell Publishing.
10.1128/9781555816667/f0275-02_thmb.gif
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Image of Figure 7.
Figure 7.

Western blot analysis of HmsR and HmsS protein levels in strains after growth at 26°Cor 37°C. Equal concentrations of whole-cell lysates were separated by sodium dodecyl sul-fate-polyacrylamide gel electrophoresis; immunoblots were reacted with antiserum against the indicated Hms proteins. The negative control lane has a whole-cell lysate from a mutant that lacks 102 kb of chromosomal DNA that includes the operon. Modified and reproduced from Kirillina et al. ( ) with permission of Blackwell Publishing.

Citation: Perry R, Bobrov A. 2010. Role of Cyclic Di-GMP in Biofilm Development and Signaling in , p 270-281. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch18
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References

/content/book/10.1128/9781555816667.ch18
1. Amikam, D., and, M. Y. Galperin. 2006. PilZ domain is part of the bacterial c-di-GMP binding protein. Bioinformatics 22: 3– 6.
2. Bacot, A. W. 1915. LXXXI. Further notes on the mechanism of the transmission of plague by fleas. J. Hyg. 14 (Plague Suppl. 4): 774– 776.
3. Bacot, A. W., and, C. J. Martin. 1914. LXVII. Observations on the mechanism of the transmission of plague by fleas. J. Hyg. 13 (Plague Suppl. 3): 423– 439.
4. Bazanova, L. P.,, I. Zhovtyi,, M. P. Maevskii,, V. T. Klimov, and, A. F. Popkov. 1991. The seasonal dynamics of blocking in the flea Citellophorus tesquorum altaicus from the Tuva natural plague focus. Med. Parazitol. (Moscow) Jan-Feb: 24– 26.
5. Blair, D. E.,, A. W. Schuttelkopf,, J. I. MacRae, and, D. M. F. van Aalten. 2005. Structure and metal-dependent mechanism of peptidoglycan deacetylase, a streptococcal virulence factor. Proc. Natl. Acad. Sci. USA 102: 15429– 15434.
6. Bobrov, A. G.,, O. Kirillina,, S. Forman,, D. Mack, and, R. D. Perry. 2008. Insights into Yersinia pestis biofilm development: topology and co-interaction of Hms inner membrane proteins involved in biofilm exopolysaccharide production. Environ. Microbiol. 10: 1419– 1432.
7. Bobrov, A. G.,, O. Kirillina, and, R. D. Perry. 2005. The phosphodiesterase activity of the HmsP EAL domain is required for negative regulation of biofilm formation in Yersinia pestis. FEMS Microbiol. Lett. 247: 123– 130.
8. Bobrov, A. G.,, O. Kirillina, and, R. D. Perry. 2007. Regulation of biofilm formation in Yersinia pestis. Adv. Exp. Med. Biol. 603: 201– 210.
9. Burroughs, A. L. 1947. Sylvatic plague studies. The vector efficiency of nine species of fleas compared with Xenopsylla cheopis. J. Hyg. 45: 371– 396.
10. Ciocchini, A. E.,, M. S. Roset,, G. Briones,, N. I. de Iannino, and, R. A. Ugalde. 2006. Identification of active site residues of the inverting glycosyltransferase Cgs required for the synthesis of cyclic β-1,2-glucan, a Brucella abortus virulence factor. Glycobiology 16: 679– 691.
11. Ciocchini, A. E.,, M. S. Roset,, N. Inon de Iannino, and, R. A. Ugalde. 2004. Membrane topology analysis of cyclic glucan synthase, a virulence determinant of Brucella abortus. J. Bacteriol. 186: 7205– 7213.
12. Cotter, P. A., and, S. Stibitz. 2007. c-di-GMP-mediated regulation of virulence and biofilm formation. Curr. Opin. Microbiol. 10: 17– 23.
13. Darby, C.,, J. W. Hsu,, N. Ghori, and, S. Falkow. 2002. Caenorhabditis elegans: plague bacteria biofilm blocks food intake. Nature 417: 243– 244.
14. Degtiareva, L. V.,, N. F. Labunets,, S. P. Osipova, and, V. I. Shchedrin. 1990. The ability of flea species on the common vole from mountainous Dagestan to transmit and preserve the causative agent of plague. Parazitologiia 24: 106– 112. (In Russian.)
15. Deng, W.,, V. Burland,, G. Plunkett III,, A. Boutin,, G. F. Mayhew,, P. Liss,, N. T. Perna,, D. J. Rose,, B. Mau,, S. Zhou,, D. C. Schwartz,, J. D. Fetherston,, L. E. Lindler,, R. R. Brubaker,, G. V. Plano,, S. C. Straley,, K. A. McDonough,, M. L. Nilles,, J. S. Matson,, F. R. Blattner, and, R. D. Perry. 2002. Genome sequence of Yersinia pestis KIM. J. Bacteriol. 184: 4601– 4611.
16. Eisen, R.,, J. Borchert,, J. Holmes,, G. Amatre,, K. Van Wyk,, R. Enscore,, N. Babi,, L. A. Atiku,, A. Wilder,, S. Vetter,, S. Bearden,, J. Montenieri, and, K. Gage. 2008. Early-phase transmission of Yersinia pestis by cat fleas ( Ctenocephalides felis) and their potential role as vectors in a plague endemic region of Uganda. Am. J. Trop. Med. Hyg. 78: 949– 956.
17. Eisen, R. J.,, S. W. Bearden,, A. P. Wilder,, J. A. Montenieri,, M. F. Antolin, and, K. L. Gage. 2006. Early-phase transmission of Yersinia pestis by unblocked fleas as a mechanism explaining rapidly spreading plague epizootics. Proc. Natl. Acad. Sci. USA 103: 15380– 15385.
18. Eisen, R. J.,, J. L. Lowell,, J. A. Montenieri,, S. W. Bearden, and, K. L. Gage. 2007. Temporal dynamics of early-phase transmission of Yersinia pestis by unblocked fleas: secondary infectious feeds prolong efficient transmission by Oropsylla montana (Siphonaptera: Ceratophyllidae). J. Med. Entomol. 44: 672– 677.
19. Eisen, R. J.,, A. P. Wilder,, S. W. Bearden,, J. A. Montenieri, and, K. L. Gage. 2007. Early-phase transmission of Yersinia pestis by unblocked Xenopsylla cheopis (Siphonaptera: Pulicidae) is as efficient as transmission by blocked fleas. J. Med. Entomol. 44: 678– 682.
20. Engelthaler, D. M.,, B. J. Hinnebusch,, C. M. Rittner, and, K. L. Gage. 2000. Quantitative competitive PCR as a technique for exploring flea- Yersinia pestis dynamics. Am. J. Trop. Med. Hyg. 62: 552– 560.
21. Forman, S.,, A. G. Bobrov,, O. Kirillina,, S. K. Craig,, J. Abney,, J. D. Fetherston, and, R. D. Perry. 2006. Identification of critical amino acid residues in the plague biofilm Hms proteins. Microbiology 152: 3399– 3410.
22. Furukawa, S.,, S. L. Kuchma, and, G. A. O’Toole. 2006. Keeping their options open: acute versus persistent infections. J. Bacteriol. 188: 1211– 1217.
23. Gage, K. L., and, M. Y. Kosoy. 2005. Natural history of plague: perspectives from more than a century of research. Annu. Rev. Entomol. 50: 505– 528.
24. Gan, N. V.,, G. A. Voronova,, L. N. Iuzvik, and, V. A. Beliaeva. 1990. The efficiency of Rhadinopsylla rothschildi and R. dahurica fleas as vectors of the causative agent of plague in a Transbaikal natural focus. Parazitologiia 24: 151– 154. (In Russian.)
25. Goller, C.,, X. Wang,, Y. Itoh, and, T. Romeo. 2006. The cation-responsive protein NhaR of Escherichia coli activates pgaABCD transcription, required for production of the biofilm adhesin poly-β-1,6-N-acetyl-D-glucosamine. J. Bacteriol. 188: 8022– 8032.
26. Goodman, A. L.,, B. Kulasekara,, A. Rietsch,, D. Boyd,, R. S. Smith, and, S. Lory. 2004. A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa. Dev. Cell 7: 745– 754.
27. Hare, J. M., and, K. A. McDonough. 1999. High-frequency RecA-dependent and -independent mechanisms of Congo red binding mutations in Yersinia pestis. J. Bacteriol. 181: 4896– 4904.
28. Heldermon, C.,, P. L. DeAngelis, and, P. H. Weigel. 2001. Topological organization of the hyaluronan synthase from Streptococcus pyogenes. J. Biol. Chem. 276: 2037– 2046.
29. Hinnebusch, B. J.,, R. D. Perry, and, T. G. Schwan. 1996. Role of the Yersinia pestis hemin storage ( hms) locus in the transmission of plague by fleas. Science 273: 367– 370.
30. Hisert, K. B.,, M. MacCoss,, M. U. Shiloh,, K. H. Darwin,, S. Singh,, R. A. Jones,, S. Ehrt,, Z. Zhang,, B. Gaffney,, S. Gandotra,, D. W. Holden,, D. Murray, and, C. Nathan. 2005. A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMP. Mol. Microbiol. 56: 1234– 1245.
31. Itoh, Y.,, J. D. Rice,, C. Goller,, A. Pannuri,, J. Taylor,, J. Meisner,, T. J. Beveridge,, J. F. Preston III, and, T. Romeo. 2008. Roles of pgaABCD genes in synthesis, modification, and export of the Escherichia coli biofilm adhesin poly-β-1,6-N-acetyl-D-glucosamine. J. Bacteriol. 190: 3670– 3680.
32. Izano, E. A.,, I. Sadovskaya,, E. Vinogradov,, M. H. Mulks,, K. Velliyagounder,, C. Ragunath,, W. B. Kher,, N. Ramasubbu,, S. Jabbouri,, M. B. Perry, and, J. B. Kaplan. 2007. Poly-N-acetylglucosamine mediates biofilm formation and antibiotic resistance in Actinobacillus pleuropneumoniae. Microb. Pathog. 43: 1– 9.
33. Jackson, S., and, T. W. Burrows. 1956. The pigmentation of Pasteurella pestis on a defined medium containing haemin. Br. J. Exp. Pathol. 37: 570– 576.
34. Jarrett, C. O.,, E. Deak,, K. E. Isherwood,, P. C. Oyston,, E. R. Fischer,, A. R. Whitney,, S. D. Kobayashi,, F. R. DeLeo, and, B. J. Hinnebusch. 2004. Transmission of Yersinia pestis from an infectious biofilm in the flea vector. J. Infect. Dis. 190: 783– 792.
35. Jenal, U., and, J. Malone. 2006. Mechanisms of cyclic-di-GMP signaling in bacteria. Annu. Rev. Genet. 40: 385– 407.
36. Jones, H. A.,, J. W. Lillard, Jr., and, R. D. Perry. 1999. HmsT, a protein essential for expression of the haemin storage (Hms +) phenotype of Yersinia pestis. Microbiology 145: 2117– 2128.
37. Kaplan, J. B.,, K. Velliyagounder,, C. Ragunath,, H. Rohde,, D. Mack,, J. K. M. Knobloch, and, N. Ramasubbu. 2004. Genes involved in the synthesis and degradation of matrix polysaccharide in Actinobacillus actinomycetemcomitans and Actino-bacillus pleuropneumoniae biofilms. J. Bacteriol. 186: 8213– 8220.
38. Kartman, L., and, F. M. Prince. 1956. Studies on Pasteurella pestis in fleas. V. The experimental plague-vector efficiency of wild rodent fleas compared with Xenopsylla cheopis, together with observations on the influence of temperature. Am. J. Trop. Med. Hyg. 5: 1058– 1070.
39. Kartman, L.,, F. M. Prince,, S. F. Quan, and, H. E. Stark. 1958. New knowledge on the ecology of sylvatic plague. Ann. N. Y. Acad. Sci. 70: 668– 711.
40. Kirillina, O.,, J. D. Fetherston,, A. G. Bobrov,, J. Abney, and, R. D. Perry. 2004. HmsP, a putative phosphodiesterase, and HmsT, a putative diguanylate cyclase, control Hms-dependent biofilm formation in Yersinia pestis. Mol. Microbiol. 54: 75– 88.
41. Kulasakara, H.,, V. Lee,, A. Brencic,, N. Liberati,, J. Urbach,, S. Miyata,, D. G. Lee,, A. N. Neely,, M. Hyodo,, Y. Hayakawa,, F. M. Ausubel, and, S. Lory. 2006. Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence. Proc. Natl. Acad. Sci. USA 103: 2839– 2844.
42. Kutyrev,, V. V.,, A. A. Filippov,, O. S. Oparina, and, O. A. Protsenko. 1992. Analysis of Yersinia pestis chromosomal determinants Pgm + and Pst s associated with virulence. Microb. Pathog. 12: 177– 186.
43. Leigh, S. A.,, S. Forman,, R. D. Perry, and, S. C. Straley. 2005. Unexpected results from the application of signature-tagged mutagenesis to identify Yersinia pestis genes required for adherence and invasion. Microb. Pathog. 38: 259– 266.
44. Lestrate, P.,, A. Dricot,, R.-M., Delrue,, C. Lambert,, V. Martinelli,, X. De Bolle,, J.-J. Letesson, and, A. Tibor. 2003. Attenuated signature-tagged mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice. Infect. Immun. 71: 7053– 7060.
45. Lillard, J. W., Jr.,, S. W. Bearden,, J. D. Fetherston, and R. D.Perry. 1999. The haemin storage (Hms +) phenotype of Yersinia pestis is not essential for the pathogenesis of bubonic plague in mammals. Microbiology 145: 197– 209.
46. Lillard, J. W., Jr.,, J. D. Fetherston,, L. Pedersen,, M. L. Pendrak, and, R. D. Perry. 1997. Sequence and genetic analysis of the hemin storage ( hms) system of Yersinia pestis. Gene 193: 13– 21.
47. Mack, D.,, W. Fischer,, A. Krokotsch,, K. Leopold,, R. Hartmann,, H. Egge, and, R. Laufs. 1996. The intercellular adhesin involved in biofilm accumulation of Staphylococcus epidermidis is a linear β-1,6-linked glucosaminoglycan: purification and structural analysis. J. Bacteriol. 178: 175– 183.
48. Mack, D.,, J. Riedewald,, H. Rohde,, T. Magnus,, H. H. Feucht,, H.-A., Elsner,, R. Laufs, and, M. E. Rupp. 1999. Essential functional role of the polysaccharide intercellular adhesin of Staphylococcus epidermidis in hemagglutination. Infect. Immun. 67: 1004– 1008.
49. Marceau, M.,, F. Sebbane,, F. Ewann,, F. Collyn,, B. Lindner,, M. A. Campos,, J.-A. Bengoechea, and, M. Simonet. 2004. The pmrF polymyxin-resistance operon of Yersinia pseudotuberculosis is upregulated by the PhoP-PhoQ two-component system but not by PmrA-PmrB, and is not required for virulence. Microbiology 150: 3947– 3957.
50. Merkel, T. J.,, S. Stibitz,, J. M. Keith,, M. Leef, and, R. Shahin. 1998. Contribution of regulation by the bvg locus to respiratory infection of mice by Bordetella pertussis. Infect. Immun. 66: 4367– 4373.
51. Patel, C. N.,, B. W. Wortham,, J. L. Lines,, J. D. Fetherston,, R. D. Perry, and, M. A. Oliveira. 2006. Polyamines are essential for the formation of plague biofilm. J. Bacteriol. 188: 2355– 2363.
52. Perry, R. D.,, A. G. Bobrov,, O. Kirillina,, H. A. Jones,, L. L. Pedersen,, J. Abney, and, J. D. Fetherston. 2004. Temperature regulation of the hemin storage (Hms +) phenotype of Yersinia pestis is posttranscriptional. J. Bacteriol. 186: 1638– 1647.
53. Perry, R. D., and, J. D. Fetherston. 1997. Yersinia pestis—etiologic agent of plague. Clin. Microbiol. Rev. 10: 35– 66.
54. Perry, R. D.,, M. L. Pendrak, and, P. Schuetze. 1990. Identification and cloning of a hemin storage locus involved in the pigmentation phenotype of Yersinia pestis. J. Bacteriol. 172: 5929– 5937.
55. Poland, J. D.,, T. J. Quan, and, A. M. Barnes. 1994. Plague, p. 93–112. In G. W. Beran (ed.), CRC Handbook Series in Zoonoses, 2nd ed. Section A: Bacterial, Rickettsial, and Mycotic Diseases. CRC Press, Inc., Ann Arbor, MI.
56. Pollitzer, R. 1954. Plague. Monogr. Ser. World Health Organ. 22: 1– 698.
57. Pratt, J. T.,, R. Tamayo,, A. D. Tischler, and, A. Camilli. 2007. PilZ domain proteins bind cyclic diguanylate and regulate diverse processes in Vibrio cholerae. J. Biol. Chem. 282: 12860– 12870.
58. Ramelot, T. A.,, A. Yee,, J. R. Cort,, A. Semesi,, C. H. Arrowsmith, and, M. A. Kennedy. 2007. NMR structure and binding studies confirm that PA4608 from Pseudomonas aeruginosa is a PilZ domain and a c-di-GMP binding protein. Proteins 66: 266– 271.
59. Römling, U.,, M. Gomelsky, and, M. Y. Galperin. 2005. c-di-GMP: the dawning of a novel bacterial signalling system. Mol. Microbiol. 57: 629– 639.
60. Ross, P.,, Y. Aloni,, H. Weinhouse,, D. Michaeli,, P. Weinberger-Ohana,, R. Mayer, and, M. Benziman. 1986. Control of cellulose synthesis in Acetobacter xylinum. A unique guanyl oli-gonucleotide is the immediate activator of the cellulose synthase. Carbohydr. Res. 149: 101– 117.
61. Ross, P.,, R. Mayer,, H. Weinhouse,, D. Amikam,, Y. Huggirat,, M. Benziman,, E. de Vroom,, A. Fidder,, P. de Paus,, L. A. J., M. Sliedregt,, G. A. van der Marel, and, J. H. van Boom. 1990. The cyclic diguanylic acid regulatory system of cellulose synthesis in Acetobacter xylinum. Chemical synthesis and biological activity of cyclic nucleotide dimer, trimer, and phospho-thioate derivatives. J. Biol. Chem. 265: 18933– 18943.
62. Ross, P.,, H. Weinhouse,, Y. Aloni,, D. Michaeli,, P. Weinberger-Ohana,, R. Mayer,, S. Braun,, E. de Vroom,, G. A. van der Marel,, J. H. van Boom, and, M. Benziman. 1987. Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid. Nature 325: 279– 281.
63. Ryan, R. P.,, Y. Fouhy,, J. F. Lucey,, L. C. Crossman,, S. Spiro,, Y.-W., He,, L.-H., Zhang,, S. Heeb,, M. Cámara,, P. Williams, and, J. M. Dow. 2006. Cell-cell signaling in Xanthomonas campestris involves an HD-GYP domain protein that functions incyclic di-GMP turnover. Proc. Natl. Acad. Sci. USA 103: 6712– 6717.
64. Ryan, R. P.,, Y. Fouhy,, J. F. Lucey,, B.-L. Jiang,, Y.-Q. He,, J.-X. Feng,, J.-L. Tang, and, J. M. Dow. 2007. Cyclic di-GMP signalling in the virulence and environmental adaptation of Xanthomonas campestris. Mol. Microbiol. 63: 429– 442.
65. Ryjenkov, D. A.,, R. Simm,, U. Römling, and, M. Gomelsky. 2006. The PilZ domain is a receptor for the second messenger c-di-GMP. The PilZ domain protein YcgR controls motility in enterobacteria. J. Biol. Chem. 281: 30310– 30314.
66. Saxena, I. M.,, J. Brown,, R. Malcolm, and, T. Dandekar. 2001. Structure-function characterization of cellulose synthase: relationship to other glycosyltransferases. Phytochemistry 57: 1135– 1148.
67. Simm, R.,, J. D. Fetherston,, A. Kader,, U. Römling, and, R. D. Perry. 2005. Phenotypic convergence mediated by GGDEF-domain-containing proteins. J. Bacteriol. 187: 6816– 6823.
68. Sun, Y.-C.,, A. Koumoutsi, and, C. Darby. 2009. The response regulator PhoP negatively regulates Yersinia pseudotuberculosis and Yersinia pestis biofilms. FEMS Microbiol. Lett. 290: 85– 90.
69. Surgalla, M. J., and, E. D. Beesley. 1969. Congo red-agar plating medium for detecting pigmentation in Pasteurella pestis. Appl. Microbiol. 18: 834– 837.
70. Tamayo, R.,, J. T. Pratt, and, A. Camilli. 2007. Roles of cyclic diguanylate in the regulation of bacterial pathogenesis. Annu. Rev. Microbiol. 61: 131– 148.
71. Tamayo, R.,, S. Schild,, J. T. Pratt, and, A. Camilli. 2008. Role of cyclic di-GMP during El Tor biotype Vibrio cholerae infection: characterization of the in vivo-induced cyclic di-GMP phosphodiesterase CdpA. Infect. Immun. 76: 1617– 1627.
72. Tischler, A. D., and, A. Camilli. 2005. Cyclic diguanylate regulates Vibrio cholerae virulence gene expression. Infect. Immun. 73: 5873– 5882.
73. Tischler, A. D.,, S. H. Lee, and, A. Camilli. 2002. The Vibrio cholerae vieSAB locus encodes a pathway contributing to cholera toxin production. J. Bacteriol. 184: 4104– 4113.
74. Voronova, G. A. 1989. Enhanced blocking capacity of the plague microbe in the body of the flea. Parazitologiia 23: 427429. (In Russian.)
75. Vuong, C.,, S. Kocianova,, J. M. Voyich,, Y. Yao,, E. R. Fischer,, F. R. DeLeo, and, M. Otto. 2004. A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence. J. Biol. Chem. 279: 54881– 54886.
76. Wang, X.,, J. F. Preston III, and, T. Romeo. 2004. The pga-ABCD locus of Escherichia coli promotes the synthesis of a polysaccharide adhesin required for biofilm formation. J. Bacteriol. 186: 2724– 2734.
77. Webb, C. T.,, C. P. Brooks,, K. L. Gage, and, M. F. Antolin. 2006. Classic flea-borne transmission does not drive plague epizootics in prairie dogs. Proc. Natl. Acad. Sci. USA 103: 6236– 6241.
78. Weinhouse, H.,, S. Sapir,, D. Amikam,, Y. Shilo,, G. Volman,, P. Ohana, and, M. Benziman. 1997. c-di-GMP-binding protein, a new factor regulating cellulose synthesis in Acetobacter xylinum. FEBS Lett. 416: 207– 211.
79. Wilder, A. P.,, R. J. Eisen,, S. W. Bearden,, J. A. Montenieri,, K. L. Gage, and, M. F. Antolin. 2008. Oropsylla hirsuta (Siphonaptera: Ceratophyllidae) can support plague epizootics in black-tailed prairie dogs ( Cynomys ludovicianus) by early-phase transmission of Yersinia pestis. Vector-Borne Zoonotic Dis. 8: 359– 368.
80. Wilder, A. P.,, R. J. Eisen,, S. W. Bearden,, J. A. Montenieri,, D. W. Tripp,, R. J. Brinkerhoff,, K. L. Gage, and, M. F. Antolin. 2008. Transmission efficiency of two flea species ( Oropsylla tuberculata cynomuris and Oropsylla hirsuta) involved in plague epizootics among prairie dogs. EcoHealth 5: 205– 212.
81. Winfield, M. D.,, T. Latifi, and, E. A. Groisman. 2005. Transcriptional regulation of the 4-amino-4-deoxy-L-arabinose biosynthetic genes in Yersinia pestis. J. Biol. Chem. 280: 14765– 14772.
82. Wolfe, A. J., and, K. L. Visick. 2008. Get the message out: cyclic-di-GMP regulates multiple levels of flagellum-based motility. J. Bacteriol. 190: 463– 475.
83. World Health Organization. 2000, posting date. WHO report on global surveillance of epidemic-prone infectious diseases. World Health Organization, Geneva, Switzerland. http://www.who.int/csr/resources/publications/surveillance/WHO_CDS.CSR_ISR_2000_1/en/.

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