Chapter 2 : Chronic versus Acute Infection States

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Chronic versus Acute Infection States, Page 1 of 2

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This chapter reviews the observations supporting the idea that acute and chronic infections represent distinct modes of host-pathogen interaction. The virulence factors associated with acute infections and chronic infections are discussed, with a focus on data obtained from human subject-based studies, when possible. expresses many virulence factors that can damage host cells and which contribute to infection in both humans and animal models. Ectopic expression of virulence factor regulator (Vfr) in strains restored expression of ExoS, type IV pilus (TFP), and elastase, confirming that downregulation of Vfr is responsible for decreased virulence factor expression in mucoid strains under the conditions evaluated in this study. While it is clear that regulators of TFP biogenesis and function are intimately associated with the control of Vfr and cyclic AMP (cAMP) expression, the mechanism that links twitching motility and Vfr remains to be elucidated. rsmZ and rsmY are two sRNAs that interact with the RNA binding protein RsmA. The paper by Bordi and coworkers also provides the first data that rsmY and rsmZ are not functionally redundant. Increased expression of T6SS genes, whose translation is negatively regulated by RsmA, specifically requires increased expression of the rsmZ sRNA. Most bacterial pathogens, included, use their virulence factors for the primary purpose of gaining access to nutrients rather than for causing damage to specific hosts. The chapter focuses on a few examples of regulatory networks that broadly impact virulence factor expression.

Citation: Kazmierczak B, Murray T. 2013. Chronic versus Acute Infection States, p 21-39. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch2
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Figure 1

Vfr-cAMP dependent regulation of virulence factor expression. CyaB is the predominate adenylate cyclase that generates cAMP, which activates transcription of virulence genes upon binding to Vfr. Vfr also activates lasR transcription in a cAMP-independent fashion. The TFP biogenesis factors FimV, FimL, and ChpA all positively regulate Vfr-cAMP. FimL affects Vfr levels during growth on agar surfaces when TFP-dependent motility is high. MucA is a negative regulator of AlgU, which itself negatively regulates Vfr via AlgR. CpdA is a phosphodiesterase that breaks down cAMP. doi:10.1128/9781555818524.ch2f1

Citation: Kazmierczak B, Murray T. 2013. Chronic versus Acute Infection States, p 21-39. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch2
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Figure 2

Expression of genes associated with chronic infection by the GacS/A two-component system. GacA activation by the GacS results in GacA phosphorylation, dimerization, and (presumably) binding to the and promoters. The and sRNAs bind to and sequester RsmA, thereby allowing translation of mRNAs encoding T6SS genes and enzymes involved in Psl (and Pel) EPS synthesis and secretion. Hypothetical negative regulators of the T3SS are presumably also expressed under these conditions. The grey molecule represents one of the three sensor kinases (PA1611, PA1976, and PA2824) shown to phosphorylate HptB in vitro. Phosphorylated HptB can phosphorylate and thereby activate the serine/threonine phosphatase activity of PA3346, for which PA3347 is a substrate. Dephosphorylation of PA3347 is hypothesized to favor sequestration of an anti-sigma factor, thereby allowing a putative sigma factor to bind to and activate the promoter. RetS is presumably inactive (dimerized?) under these conditions. Proteins whose deletion inhibits chronic gene expression are colored blue; those whose deletion favors chronic gene expression are colored red. Sensor kinase domains are schematized as follows: HK domains, rectangles; receiver domains, diamonds; and histidine phosphotransfer domains, circles. Yellow circles indicate domains with phosphoacceptor histidines or aspartates, while curved blue arrows indicate phosphotransfer reactions documented in vitro. The functions of LadS in this signaling pathway are not established. IM, inner membrane. doi:10.1128/9781555818524.ch2f2

Citation: Kazmierczak B, Murray T. 2013. Chronic versus Acute Infection States, p 21-39. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch2
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Figure 3

Expression of genes associated with acute infection by the GacS/A two-component system. Binding of an unknown ligand to the periplasmic domain of RetS is hypothesized to disrupt RetS homodimerization and to increase the likelihood of RetS-GacS interactions, which inhibit GacS autophosphorylation and phosphotransfer to GacA. Under these conditions, sRNA transcript levels are low and free RsmA can bind to target mRNAs, including those encoding T6SS genes and the operon. Blue arrows indicate phosphotransfer reactions that occur in vitro; their occurrence as an in vivo signaling pathway is speculative but based on the phenotypes of bacteria in which these gene products (RetS, HptB, PA3346, and PA3347) are not expressed. IM, inner membrane. doi:10.1128/9781555818524.ch2f3

Citation: Kazmierczak B, Murray T. 2013. Chronic versus Acute Infection States, p 21-39. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch2
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1. Abdou, L.,, H. T. Chou,, D. Haas,, and C. D. Lu. 2011. Promoter recognition and activation by the global response regulator CbrB in Pseudomonas aeruginosa. J. Bacteriol. 193:27842792.
2. Beatson, S.,, C. B. Whitchurch,, J. L. Sargent,, R. C. Levesque,, and J. S. Mattick. 2002. Differential regulation of twitching motility and elastase production by Vfr in Pseudomonas aeruginosa. J. Bacteriol. 184:36053613.
3. Bianconi, I.,, A. Milani,, C. Cigana,, M. Paroni,, R. C. Levesque,, G. Bertoni,, and A. Bragonzi. 2011. Positive signature-tagged mutagenesis in Pseudomonas aeruginosa: tracking patho-adaptive mutations promoting airways chronic infection. PLoS Pathog. 7:e1001270.
4. Bjarnsholt, T.,, P. O. Jensen,, M. J. FIandaca,, J. Pedersen,, C. R. Hansen,, C. B. Andersen,, T. Pressler,, M. Givskov,, and N. Hoiby. 2009. Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr. Pulmonol. 44:547558.
5. Bjarnsholt, T.,, P. O. Jensen,, T. H. Jakobsen,, R. Phipps,, A. K. Nielsen,, M. T. Rybtke,, T. Tolker-Nielsen,, M. Givskov,, N. Hoiby,, O. Ciofu, and the Scandinavian Cystic Fibrosis Study Consortium. 2010. Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients. PLoS One 5:e10115.
6. Bodey, G. P. 2009. Fever and neutropenia: the early years. J.Antimicrob. Chemother. 63(Suppl. 1):i3i13.
7. Bordi, C.,, M.-C. Lamy,, I. Ventre,, E. Termine,, A. Hachani,, S. Fillet,, B. Roche,, S. Bleves,, V. Mejean,, A. Lazdunski,, and A. Filloux. 2010. Regulatory RNAs and HptB/RetS signalling pathways fine-tune Pseudomonas aeruginosa pathogenesis. Mol. Microbiol. 76:14271443.
8. Bragonzi, A.,, M. Paroni,, A. Nonis,, N. Cramer,, S. Montanari,, J. Rejman,, C. Di Serio,, G. Doring,, and B. Tummler. 2009. Pseudomonas aeruginosa microevolution during cystic fibrosis lung infection establishes clones with adapted virulence. Am. J. Respir. Crit. Care Med. 180:138145.
9. Brencic, A.,, and S. Lory. 2009. Determination of the regulon and identification of novel mRNA targets of Pseudomonas aeruginosa RsmA. Mol. Microbiol. 72:612632.
10. Brencic, A.,, K. A. McFarland,, H. R. McManus,, S. Castang,, I. Mogno,, S. L. Dove,, and S. Lory. 2009. The GacS/GacA signal transduction system of Pseudomonas aeruginosa acts exclusively through its control over the transcription of the RsmY and RsmZ regulatory small RNAs. Mol. Microbiol. 73:434445.
11. Burns, J. L.,, R. L. Gibson,, S. McNamara,, D. Yim,, J. Emerson,, M. Rosenfeld,, P. Hiatt,, K. McCoy,, R. Castile,, A. L. Smith,, and B. W. Ramsey. 2001. Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J. Infect.Dis. 183:444452.
12. Burrowes, E.,, C. Baysse,, C. Adams,, and F. O’Gara. 2006. Influence of the regulatory protein RsmA on cellular functions in Pseudomonas aeruginosa PAO1, as revealed by transcriptome analysis. Microbiology 152:405418.
13. Castang, S.,, H. R. McManus,, K. H. Turner,, and S. L. Dove. 2008. H-NS family members function coordinately in an opportunistic pathogen. Proc. Natl. Acad. Sci. USA 105:1894718952.
14. Cordes, T. J.,, G. A. Worzalla,, A. M. Ginster,, and K. T. Forest. 2011. Crystal structure of the Pseudomonas aeruginosa virulence factor regulator. J. Bacteriol. 193:40694074.
15. Croda-Garcia, G.,, V. Grosso-Becerra,, A. Gonzalez-Valdez,, L. Servin-Gonzalez,, and G. Soberon-Chavez. 2011. Transcriptional regulation of Pseudomonas aeruginosa rhlR: role of the CRP orthologue Vfr (virulence factor regulator) and quorum-sensing regulators LasR and RhlR. Microbiology 157:25452555.
16. Dacheux, D.,, O. Epaulard,, A. de Groot,, B. Guery,, R. Leberre,, I. Attree,, B. Polack,, and B. Toussaint. 2002. Activation of the Pseudomonas aeruginosa type III secretion system requires an intact pyruvate dehydrogenase aceAB operon. Infect. Immun. 70:39733977.
17. D’Argenio, D. A.,, M. Wu,, L. R. Hoffman,, H. Kulasekara,, E. Deziel,, E. E. Smith,, H. Nguyen,, R. K. Ernst,, T. J. L. Freeman,, D. H. Spencer,, M. Brittnacher,, H. S. Hayden,, S. Selgrade,, M. Klausen,, D. R. Goodlett,, J. L. Burns,, B. W. Ramsey,, and S. I. Miller. 2007. Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients. Mol. Microbiol. 64:512533.
18. Diaz, M. R.,, J. M. King,, and T. L. Yahr. 2011. Intrinsic and extrinsic regulation of type III secretion gene expression in Pseudomonas aeruginosa. Front. Microbiol. 2:89.
19. El Solh, A. A.,, M. E. Akinnusi,, J. P. Wiener-Kronish,, S. V. Lynch,, L. A. Pineda,, and K. Szarpa. 2008. Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia. Am. J. Respir. Crit. Care Med. 178:513519.
20. Engel, J.,, and P. Balachandran. 2009. Role of Pseudomonas aeruginosa type III effectors in disease. Curr. Opin. Microbiol. 12:6166.
21. Feliziani, S.,, A. M. Lujan,, A. J. Moyano,, C. Sola,, J. L. Bocco,, P. Montanaro,, L. F. Canigia,, C. E. Argarana,, and A. M. Smania. 2010. Mucoidy, quorum sensing, mismatch repair and antibiotic resistance in Pseudomonas aeruginosa from cystic fibrosis chronic airways infections. PLoS One 5:e12669.
22. Fox, A.,, D. Haas,, C. Reimmann,, S. Heeb,, A. Filloux,, and R. Voulhoux. 2008. Emergence of secretion-defective sublines of Pseudomonas aeruginosa PAO1 resulting from spontaneous mutations in the vfr global regulatory gene. Appl. Environ. Microbiol. 74:19021908.
23. Fuchs, E. L.,, E. D. Brutinel,, A. K. Jones,, N. B. Fulcher,, M. L. Urbanowski,, T. L. Yahr,, and M. C. Wolfgang. 2010b. The Pseudomonas aeruginosa Vfr regulator controls global virulence factor expression through cyclic AMP-dependent and -independent mechanisms. J. Bacteriol. 192:35533564.
24. Fuchs, E. L.,, E. D. Brutinel,, E. R. Klem,, A. R. Fehr,, T. L. Yahr,, and M. C. Wolfgang. 2010b. In vitro and in vivo characterization of the Pseudomonas aeruginosa cyclic AMP (cAMP) phosphodiesterase CpdA, required for cAMP homeostasis and virulence factor regulation. J. Bacteriol. 192:27792790.
25. Fulcher, N. B.,, P. M. Holliday,, E. Klem,, M. J. Cann,, and M. C. Wolfgang. 2010. The Pseudomonas aeruginosa Chp chemosensory system regulates intracellular cAMP levels by modulating adenylate cyclase activity. Mol. Microbiol. 76:889904.
26. Gooderham, W. J.,, M. Bains,, J. B. McPhee,, I. Wiegand,, and R. E. Hancock. 2008. Induction by cationic antimicrobial peptides and involvement in intrinsic polymyxin and antimicrobial peptide resistance, biofilm formation, and swarming motility of PsrA in Pseudomonas aeruginosa. J. Bacteriol. 190:56245634.
27. Gooderham, W. J.,, S. L. Gellatly,, F. Sanschagrin,, J. B. McPhee,, M. Bains,, C. Cosseau,, R. C. Levesque,, and R. E. Hancock. 2009. The sensor kinase PhoQ mediates virulence in Pseudomonas aeruginosa. Microbiology 155:699711.
28. Goodman, A. L.,, B. R. 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 7:745754.
29. Goodman, A. L.,, M. Merighi,, M. Hyodo,, I. Ventre,, A. Filloux,, and S. Lory. 2009. Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen. Genes Dev. 23:249259.
30. Gorke, B.,, and J. Stulke. 2008. Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat. Rev. Microbiol. 6:613624.
31. Hauser, A.,, E. Cobb,, M. Bodi,, D. Mariscal,, J. Valles,, J. Engel,, and J. Rello. 2002. Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Crit. Care Med. 30:521528.
32. Hauser, A. R. 2009. The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nat. Rev. Microbiol. 7:654665.
33. Hauser, A. R.,, M. Jain,, M. Bar-Meir,, and S. A. McColley. 2011. Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin. Microbiol. Rev. 24:2970.
34. Hoboth, C.,, R. Hoffmann,, A. Eichner,, C. Henke,, S. Schmoldt,, A. Imhof,, J. Heesemann,, and M. Hogardt. 2009. Dynamics of adaptive microevolution of hypermutable Pseudomonas aeruginosa during chronic pulmonary infection in patients with cystic fibrosis. J. Infect. Dis. 200:118130.
35. Hogardt, M.,, C. Hoboth,, S. Schmoldt,, C. Henke,, L. Bader,, and J. Heesemann. 2007. Stage-specific adaptation of hypermutable Pseudomonas aeruginosa isolates during chronic pulmonary infection in patients with cystic fibrosis. J. Infect. Dis. 195:7080.
36. Hsu, J.-L.,, H.-C. Chen,, H.-L. Peng,, and H.-Y. Chang. 2008. Characterization of the histidine-containing phosphotransfer protein B-mediated multistep phosphorelay system in Pseudomonas aeruginosa PAO1. J. Biol. Chem. 283:99339944.
37. Inclan, Y. F.,, M. J. Huseby,, and J. N. Engel. 2011. FimL regulates cAMP synthesis in Pseudomonas aeruginosa. PLoS One 6:e15867.
38. Irie, Y.,, M. Starkey,, A. N. Edwards,, D. J. Wozniak,, T. Romeo,, and M. R. Parsek. 2010. Pseudomonas aeruginosa biofilm matrix polysaccharide Psl is regulated transcriptionally by RpoS and post-transcriptionally by RsmA. Mol. Microbiol. 78:158172.
39. Jain, M.,, M. Bar-Meir,, S. McColley,, J. Cullina,, E. Potter,, C. Powers,, M. Prickett,, R. Seshadri,, B. Jovanovic,, A. Petrocheilou,, J. D. King,, and A. R. Hauser. 2008. Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis: a paradigm of chronic infection. Transl. Res. 152:257264.
40. Jing, X.,, J. Jaw,, H. H. Robinson,, and F. D. Schubot. 2010. Crystal structure and oligomeric state of the RetS signaling kinase sensory domain. Proteins 78:16311640.
41. Johansen, H. K.,, and N. Hoiby. 1992. Seasonal onset of initial colonisation and chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis in Denmark. Thorax 47:109111.
42. Jones, A. K.,, N. B. Fulcher,, G. J. Balzer,, M. L. Urbanowski,, C. L. Pritchett,, M. J. Schurr,, T. L. Yahr,, and M. C. Wolfgang. 2010. Activation of the Pseudomonas aeruginosa AlgU regulon through mucA mutation inhibits cyclic AMP/Vfr signaling. J.Bacteriol. 192:57095717.
43. Jyot, J.,, V. Balloy,, G. Jouvion,, A. Verma,, L. Touqui,, M. Huerre,, M. Chignard,, and R. Ramphal. 2011. Type II secretion system of Pseudomonas aeruginosa: in vivo evidence of a significant role in death due to lung infection. J. Infect. Dis. 203:13691377.
44. Kang, Y.,, V. V. Lunin,, T. Skarina,, A. Savchenko,, M. J. Schurr,, and T. T. Hoang. 2009. The long-chain fatty acid sensor, PsrA, modulates the expression of rpoS and the type III secretion exsCEBA operon in Pseudomonas aeruginosa. Mol. Microbiol. 73:120136.
45. Kim, T. J.,, S. Chauhan,, V. L. Motin,, E. B. Goh,, M. M. Igo,, and G. M. Young. 2007. Direct transcriptional control of the plasminogen activator gene of Yersinia pestis by the cyclic AMP receptor protein. J. Bacteriol. 189:88908900.
46. Koh, A. Y.,, G. R. Priebe,, C. Ray,, N. van Rooijen,, and G. B. Pier. 2009. Inescapable need for neutrophils as mediators of cellular innate immunity to acute Pseudomonas aeruginosa pneumonia. Infect. Immun. 77:53005310.
47. Kuchma, S. L.,, J. P. Connolly,, and G. A. O’Toole. 2005. A three-component regulatory system regulates biofilm maturation and type III secretion in Pseudomonas aeruginosa. J. Bacteriol. 187:14411454.
48. Kulasakara, H. D.,, I. Ventre,, B. R. Kulasekara,, A. Lazdunski,, A. Filloux,, and S. Lory. 2005. A novel two-component system controls the expression of Pseudomonas aeruginosa fimbrial cup genes. Mol. Microbiol. 55:368380.
49. Lapouge, K.,, M. Schubert,, F. H.-T. Allain,, and D. Haas. 2008. Gac/Rsm signal transduction pathway of g-proteobacteria: from RNA recognition to regulation of social behaviour. Mol. Microbiol. 67:241253.
50. Laskowski, M. A.,, and B. I. Kazmierczak. 2006. Mutational analysis of RetS, an unusual sensor kinase-response regulator hybrid required for Pseudomonas aeruginosa virulence. Infect. Immun. 74:44624473.
51. Laskowski, M. A.,, E. Osborn,, and B. I. Kazmierczak. 2004. A novel sensor kinase-response regulator hybrid regulates type III secretion and is required for virulence in Pseudomonas aeruginosa. Mol. Microbiol. 54:10901103.
52. Lavoie, E. G.,, T. Wangdi,, and B. I. Kazmierczak. 2011. Innate immune responses to Pseudomonas aeruginosa infection. Microbes Infect. 13:11331145.
53. Le Berre, R.,, S. Nguyen,, E. Nowak,, E. Kipnis,, M. Pierre,, L. Quenee,, F. Ader,, S. Lancel,, R. Courcol,, B. P. Guery,, and K. Faure. 2011. Relative contribution of three main virulence factors in Pseudomonas aeruginosa pneumonia. Crit. Care Med. 39:21132120.
54. Lelong, E.,, A. Marchetti,, M. Simon,, J. L. Burns,, C. van Delden,, T. Kohler,, and P. Cosson. 2011. Evolution of Pseudomonas aeruginosa virulence in infected patients revealed in a Dictyostelium discoideum host model. Clin. Microbiol. Infect. 17:14151420.
55. Linares, J. F.,, R. Moreno,, A. Fajardo,, L. Martinez-Solano,, R. Escalante,, F. Rojo,, and J. L. Martinez. 2010. The global regulator Crc modulates metabolism, susceptibility to antibiotics and virulence in Pseudomonas aeruginosa. Environ. Microbiol. 12:31963212.
56. Mathee, K.,, G. Narasimhan,, C. Valdes,, X. Qiu,, J. M. Matewish,, M. Koehrsen,, A. Rokas,, C. N. Yandava,, R. Engels,, E. Zeng,, R. Olavarietta,, M. Doud,, R. S. Smith,, P. Montgomery,, J. R. White,, P. A. Godfrey,, C. Kodira,, B. Birren,, J. E. Galagan,, and S. Lory. 2008. Dynamics of Pseudomonas aeruginosa genome evolution. Proc. Natl. Acad. Sci. USA 105:31003105.
57. McPhee, J. B.,, M. Bains,, G. Winsor,, S. Lewenza,, A. Kwasnicka,, M. D. Brazas,, F. S. Brinkman,, and R. E. Hancock. 2006. Contribution of the PhoP-PhoQ and PmrA-PmrB two-component regulatory systems to Mg2+-induced gene regulation in Pseudomonas aeruginosa. J. Bacteriol. 188:39954006.
58. Michel, G. P.,, A. Aguzzi,, G. Ball,, C. Soscia,, S. Bleves,, and R. Voulhoux. 2011. Role of fimV in type II secretion system-dependent protein secretion of Pseudomonas aeruginosa on solid medium. Microbiology 157:19451954.
59. Moreno, R.,, M. Martinez-Gomariz,, L. Yuste,, C. Gil,, and F. Rojo. 2009a. The Pseudomonas putida Crc global regulator controls the hierarchical assimilation of amino acids in a complete medium: evidence from proteomic and genomic analyses. Proteomics 9:29102928.
60. Moreno, R.,, S. Marzi,, P. Romby,, and F. Rojo. 2009b. The Crc global regulator binds to an unpaired A-rich motif at the Pseudomonas putida alkS mRNA coding sequence and inhibits translation initiation. Nucleic Acids Res. 37:76787690.
61. Moreno, R.,, A. Ruiz-Manzano,, L. Yuste,, and F. Rojo. 2007. The Pseudomonas putida Crc global regulator is an RNA binding protein that inhibits translation of the AlkS transcriptional regulator. Mol. Microbiol. 64:665675.
62. Nishijyo, T.,, D. Haas,, and Y. Itoh. 2001. The CbrA-CbrB two-component regulatory system controls the utilization of multiple carbon and nitrogen sources in Pseudomonas aeruginosa. Mol. Microbiol. 40:917931.
63. Ostroff, R. M.,, B. Wretlind,, and M. L. Vasil. 1989. Mutations in the hemolytic-phospholipase C operon result in decreased virulence of Pseudomonas aeruginosa PAO1 grown under phosphate-limiting conditions. Infect. Immun. 57:13691373.
64. Palmer, K. L.,, L. M. Aye,, and M. Whiteley. 2007. Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum. J. Bacteriol. 189:80798087.
65. Rau, M. H.,, S. K. Hansen,, H. K. Johansen,, L. E. Thomsen,, C. T. Workman,, K. F. Nielsen,, L. Jelsbak,, N. Hoiby,, L. Yang,, and S. Molin. 2010. Early adaptive developments of Pseudomonas aeruginosa after the transition from life in the environment to persistent colonization in the airways of human cystic fibrosis hosts. Environ. Microbiol. 12:16431658.
66. Rietsch, A.,, and J. J. Mekalanos. 2006. Metabolic regulation of type III secretion gene expression in Pseudomonas aeruginosa. Mol. Microbiol. 59:807820.
67. Rietsch, A.,, M. C. Wolfgang,, and J. J. Mekalanos. 2004. Effect of metabolic imbalance on expression of type III secretion genes in Pseudomonas aeruginosa. Infect. Immun. 72:13831890.
68. Rojo, F. 2010. Carbon catabolite repression in Pseudomonas: optimizing metabolic versatility and interactions with the environment. FEMS Microbiol. Rev. 34:658684.
69. Romeo, T.,, G. M,, M. Y. Liu,, and A. M. Brun-Zinkernagel. 1993. Identification and molecular characterization of csrA, a pleiotropic gene from Escherichia coli that affects glycogen biosynthesis, gluconeogenesis, cell size, and surface properties. J. Bacteriol. 175:47444755.
70. Romling, U.,, B. Fiedler,, J. Bosshammer,, D. Grothues,, J. Greipel,, H. von der Hardt,, and B. Tummler. 1994. Epidemiology of chronic Pseudomonas aeruginosa infections in cystic fibrosis. J. Infect. Dis. 170:16161621.
71. Roy-Burman, A.,, R. H. Savel,, S. Racine,, B. L. Swanson,, N. S. Revadigar,, J. Fujimoto,, T. Sawa,, D. W. Frank,, and J. P. Wiener-Kronish. 2001. Type III protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections. J. Infect. Dis. 183:17671774.
72. Schmoll, T.,, M. Ott,, B. Oudega,, and J. Hacker. 1990. Use of a wild-type gene fusion to determine the influence of environmental conditions on expression of the S fimbrial adhesin in an Escherichia coli pathogen. J. Bacteriol. 172:51035111.
73. Semmler, A. B.,, C. B. Whitchurch,, A. J. Leech,, and J. S. Mattick. 2000. Identification of a novel gene, fimV, involved in twitching motility in Pseudomonas aeruginosa. Microbiology 146:13211332.
74. Serate, J.,, G. P. Roberts,, O. Berg,, and H. Youn. 2011. Ligand responses of Vfr, the virulence factor regulator from Pseudomonas aeruginosa. J. Bacteriol. 193:48594868.
75. Shen, D. K.,, D. Filopon,, L. Kuhn,, B. Polack,, and B. Toussaint. 2006. PsrA is a positive transcriptional regulator of the type III secretion system in Pseudomonas aeruginosa. Infect. Immun. 74:11211129.
76. Shortridge, V. D.,, A. Lazdunski,, and M. L. Vasil. 1992. Osmoprotectants and phosphate regulate expression of phospholipase C in Pseudomonas aeruginosa. Mol. Microbiol. 6:863871.
77. Smith, E. E.,, D. G. Buckley,, Z. Wu,, C. Saenphimmachak,, L. R. Hoffman,, D. A. D’Argenio,, S. I. Miller,, B. W. Ramsey,, D. P. Speert,, S. M. Moskowitz,, J. L. Burns,, R. Kaul,, and M. V. Olson. 2006. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl. Acad. Sci. USA 103:84878492.
78. Smith, R. S.,, M. C. Wolfgang,, and S. Lory. 2004. An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia. Infect. Immun. 72:16771684.
79. Sonnleitner, E.,, L. Abdou,, and D. Haas. 2009. Small RNA as global regulator of carbon catabolite repression in Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA 106:2186621871.
80. Suh, S. J.,, L. J. Runyen-Janecky,, T. C. Maleniak,, P. Hager,, C. H. MacGregor,, N. A. Zielinski-Mozny,, P. V. Phibbs, Jr.,, and S. E. H. West. 2002. Effect of vfr mutation on global gene expression and catabolite repression control of Pseudomonas aeruginosa. Microbiology 148:15611569.
81. Takeuchi, K.,, P. Kiefer,, C. Reimmann,, C. Keel,, C. Dubuis,, J. Rolli,, J. A. Vorholt,, and D. Haas. 2009. Small RNA-dependent expression of secondary metabolism is controlled by Krebs cycle function in Pseudomonas fluorescens. J. Biol. Chem. 284:3497634985.
82. Teplitski, M.,, R. I. Goodier,, and B. M. M. Ahmer. 2006. Catabolite repression of the SirA regulatory cascade in Salmonella enterica. Int. J. Med. Microbiol. 296:449466.
83. Van Alst, N. E.,, M. Wellington,, V. L. Clark,, C. G. Haidaris,, and B. H. Iglewski. 2009. Nitrite reductase NirS is required for type III secretion system expression and virulence in the human monocyte cell line THP-1 by Pseudomonas aeruginosa. Infect. Immun. 77:44464454.
84. Van Devanter, D. R.,, and J. M. Van Dalfsen. 2005. How much do Pseudomonas biofilms contribute to symptoms of pulmonary exacerbation in cystic fibrosis? Pediatr. Pulmonol. 39:504506.
85. Vasil, M. L. 2007. How we learnt about iron acquisition in Pseudomonas aeruginosa: a series of very fortunate events. Biometals 20:587601.
86. Ventre, I.,, A. L. Goodman,, I. Vallet-Gely,, P. Vasseur,, C. Soscia,, S. Molin,, S. Bleves,, A. Lazdunski,, S. Lory,, and A. Filloux. 2006. Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes. Proc. Natl. Acad. Sci. USA 103:171176.
87. Vincent, F.,, A. Round,, A. Reynaud,, C. Bordi,, A. Filloux,, and Y. Bourne. 2010. Distinct oligomeric forms of the Pseudomonas aeruginosa RetS sensor domain modulate accessibility to the ligand binding site. Environ. Microbiol. 12:17751786.
88. Wargo, M. J.,, T. C. Ho,, M. J. Gross,, L. A. Whittaker,, and D. A. Hogan. 2009. GbdR regulates Pseudomonas aeruginosa plcH and pchP transcription in response to choline catabolites. Infect. Immun. 77:11031111.
89. Whitchurch, C. B.,, S. A. Beatson,, J. C. Comolli,, T. Jakobsen,, J. L. Sargent,, J. J. Bertrand,, J. West,, M. Klausen,, L. L. Waite,, P. J. Kang,, T. Tolker-Nielsen,, J. S. Mattick,, and J. N. Engel. 2005. Pseudomonas aeruginosa fimL regulates multiple virulence functions by intersecting with Vfr-modulated pathways. Mol. Microbiol. 55:13571378.
90. Wolfgang, M. C.,, V. T. Lee,, M. E. Gilmore,, and S. Lory. 2003. Coordinate regulation of bacterial genes by a novel adenylate cyclase signaling pathway. Dev. Cell 4:253263.
91. Workentine, M. L.,, L. Chang,, H. Ceri,, and R. J. Turner. 2009. The GacS-GacA two-component regulatory system of Pseudomonas fluorescens: a bacterial two-hybrid analysis. FEMS Microbiol. Lett. 292:5056.
92. Wu, W.,, H. Badrane,, S. Arora,, H. V. Baker,, and S. Jin. 2004. MucA-mediated coordination of type III secretion and alginate synthesis in Pseudomonas aeruginosa. J. Bacteriol. 186:75757585.
93. Yang, L.,, L. Jelsbak,, R. L. Marvig,, S. Damkiaer,, C. T. Workman,, M. H. Rau,, S. K. Hansen,, A. Folkesson,, H. K. Johansen,, O. Ciofu,, N. Hoiby,, M. O. Sommer,, and S. Molin. 2011. Evolutionary dynamics of bacteria in a human host environment. Proc. Natl. Acad. Sci. USA 108:74817486.
94. Yeung, A. T.,, M. Bains,, and R. E. Hancock. 2011. The sensor kinase CbrA is a global regulator that modulates metabolism, virulence, and antibiotic resistance in Pseudomonas aeruginosa. J. Bacteriol. 193:918931.
95. Yu, H.,, J. C. Boucher,, N. S. Hibler,, and V. Deretic. 1996. Virulence properties of Pseudomonas aeruginosa lacking the extreme-stress sigma factor AlgU (sE). Infect. Immun. 64:27742781.
96. Zolfaghar, I.,, A. A. Angus,, P. J. Kang,, A. To,, D. J. Evans,, and S. M. J. Fleiszig. 2005. Mutation of retS, encoding a putative hybrid two-component regulatory protein in Pseudomonas aeruginosa, attenuates multiple virulence mechanisms. Microbes Infect. 7:13051316.


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Table 1

Activities associated with T3SS effectors of

Citation: Kazmierczak B, Murray T. 2013. Chronic versus Acute Infection States, p 21-39. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch2
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Table 2

Examples of mutations accumulated by during chronic pulmonary infection in CF patients

Citation: Kazmierczak B, Murray T. 2013. Chronic versus Acute Infection States, p 21-39. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch2
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Table 3

Other regulators implicated in virulence factor expression

Citation: Kazmierczak B, Murray T. 2013. Chronic versus Acute Infection States, p 21-39. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch2

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