Chapter 19 : PrfA and the Switch from Environmental Bacterium to Intracellular Pathogen

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The facultative intracellular bacterium has been used for decades as a model infectious agent for the study of host innate and adaptive immunity. This chapter focuses on describing what is currently known about how mediates the transition from saprophyte to mammalian pathogen and explores the regulatory circuit governed by a transcriptional activator known as PrfA that allows the bacterium to flourish in both soil and cytosol. In healthy individuals, disease caused by is usually self-limiting and presents as a form of mild gastroenteritis. The primary route of infection is translocation across the intestinal epithelium following the consumption of contaminated food products. The correct compartmentalization of broad range phospholipase C (PC-PLC) activity is important for avoiding damage to host cell membranes and is a critical aspect of virulence. strains containing mutations are hyperinvasive, are quicker to mediate phagosome escape, and initiate bacterial actin-based motility more rapidly to promote cell-to-cell spread. Microarray analyses of wild-type and mutants grown in brain heart infusion broth suggest the possibility of at least 145 or more additional genes associated with PrfA regulation. PrfA activation appears to function as the switch that enables to transition from saprophyte to pathogen. In contrast to carbon sources encountered within the host, PrfA-dependent gene expression is dramatically repressed in the presence of cellobiose and other readily metabolized sugars that are likely to be more prevalent in environments located outside of host cells.

Citation: Xayarath B, Freitag N. 2013. PrfA and the Switch from Environmental Bacterium to Intracellular Pathogen, p 363-385. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch19
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Figure 1

The L. monocytogenes transition from environmental bacterium to intracellular pathogen. L. monocytogenes survives under a number of diverse ecological conditions. It can be found growing within soil, decaying vegetation, water, silage, sewage, and food processing plants, but it also has the ability to adapt to life inside mammalian host cells. Central to the L. monocytogenes transition to life inside of host cells is the activity of a transcriptional regulator known as PrfA. Outside of host cells, PrfA exists in a low-activity state and directs low levels of virulence gene expression. Once inside a host, PrfA becomes highly activated (PrfA*) and dramatically increases the expression of a number of virulence gene products required for host cell invasion (internalins InlA and InlB), lysis of the phagosomal membrane (LLO, PI-PLC, and PC-PLC), intracellular growth (Hpt), cell-to-cell spread (actin assembly via ActA and relief of cell-cell cortical tension via InlC), and the dissolution of the double membrane resulting from cell-to-cell spread (LLO, PI-PLC, and PC-PLC). Adapted from Freitag et al. 2009.doi:10.1128/9781555818524.ch19f1

Citation: Xayarath B, Freitag N. 2013. PrfA and the Switch from Environmental Bacterium to Intracellular Pathogen, p 363-385. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch19
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Figure 2

Transcriptional and posttranscriptional regulation of prfA. (A) Organization of the plcA-prfA region showing the location of all three promoter elements required for prfA expression. PprfAP1 and PprfAP2 are immediately upstream of prfA, while the third promoter, PplcA, is located upstream of plcA and directs both a monocistronic plcA transcript and a bicistronic plcAprfA transcript. Both PplcA and PprfAP1 contain characteristics of an sA-dependent promoter, while PprfAP2 contains characteristics of both sB- and sA-dependent promoters. The stem-loop structure indicates the plcA transcriptional terminator. The thermosensor is present within the 5¢ UTR of the prfAP1 transcript and inhibits prfAP1 translation at lower temperatures. Both PprfAP1 and PprfAP2 are negatively [(−)] influenced by high levels of PrfA, whereas PplcA is positively [(+)] influenced, resulting in the production of the increased quantities of PrfA required for intracellular growth and spread. (B) Model of SreA trans regulation of prfA expression. SAM binding to the SAM-responsive riboswitch SreA results in a conformational change to the transcript and a terminator structure is formed, which then leads to the production of a short transcript lacking the downstream genes. Complementary nucleotide regions shared between this sRNA transcript and the 5¢ UTR of the prfA mRNA result in a direct interaction between the two molecules that functions to reduce PrfA protein synthesis by blocking ribosome binding at 37°C. At lower temperatures (≤30°C), the thermosensor structure is formed at the 5¢ UTR of the prfA mRNA and prevents both SreA binding and prfA mRNA translation. doi:10.1128/9781555818524.ch19f2

Citation: Xayarath B, Freitag N. 2013. PrfA and the Switch from Environmental Bacterium to Intracellular Pathogen, p 363-385. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch19
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Figure 3

Model of the PrfA putative cofactor binding pocket and location of PrfA* amino acid substitutions. (A) Electrostatic modeling of PrfA protein showing the distribution of solvent-accessible surface charges on the protein dimer. Positive charge is shown in blue and negative charge in red, with electrostatic potentials ranging from –4kT/e (red) to +4kT/e (blue). Arrows point to the lysine residues that contribute to the positive charge of the putative cofactor binding pocket within PrfA. The positive charge of the DNA binding region is also highlighted at the bottom of the PrfA monomer. Reprinted from PLoS One ( ) with permission of the publisher. (B) Ribbon modeling of the PrfA dimer using DeepView-Swiss PdbViewer v4.0 (http://spdbv.vital-it.ch/) highlighting the tunnel region (black arrow) suggested by Eiting et al., 2005, as the cofactor binding site. The monomers that make up the dimer are colored either light or dark gray, and the DNA-binding helix-turn-helices are shown in blue. The locations of amino acid substitutions conferring the PrfA* phenotype are colored as follows: Y63C in green, S71C in tan, E77K in magenta, A94T in dark blue, L140F in red, G145S in black, L148P in yellow, Y154C in light pink, G155S in light blue, and P219S in orange. Residues G145 and G155 are difficult to see in this orientation and have been further highlighted by arrows pointing to their location. doi:10.1128/9781555818524.ch19f3

Citation: Xayarath B, Freitag N. 2013. PrfA and the Switch from Environmental Bacterium to Intracellular Pathogen, p 363-385. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch19
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Figure 4

The posttranslocation secretion chaperone PrsA2 is critical for L. monocytogenes viability under conditions of PrfA activation. PrsA2 is a secreted chaperone that contributes to the folding and stability of L. monocytogenes secreted virulence factors and penicillin binding proteins at the membrane-cell wall interface. Outside of host cells and under conditions of low PrfA activity, PrsA2 is synthesized in small amounts and assists in the folding of virulence factors secreted at low levels, such as LLO (top). When PrfA becomes activated following the entry of L. monocytogenes into the cytosol, protein secretion increases dramatically, with a concurrent increase in PrsA2 levels to help mediate secreted protein folding and stability (middle). Under conditions of PrfA activation in the absence of PrsA2, misfolded proteins accumulate at the membrane-cell wall interface and compromise bacterial viability within the cytosol (bottom). doi:10.1128/9781555818524.ch19f4

Citation: Xayarath B, Freitag N. 2013. PrfA and the Switch from Environmental Bacterium to Intracellular Pathogen, p 363-385. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch19
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Figure 5

Model of prfA regulation during the L. monocytogenes transition from life in the outside environment to life inside the host. In the outside environment, low levels of PrfA protein are provided via transcripts directed from both the prfAP1 and prfAP2 promoters. The prfAP1 transcript contains a 5¢ RNA thermosensor that serves to inhibit prfAP1 translation at temperatures below 30°C. Low levels of PrfA protein are provided from the prfAP2 transcripts (upper row). Following bacterial ingestion by a mammalian host, an increase in temperature and the acidic environment of the stomach induces the activity of the stress-responsive RNA polymerase alternative sigma factor sB, leading to increased expression of prfA, inlA, and inlB via their sB-regulated promoters. A low-activity form of PrfA accumulates as a result of the increase in prfAP2 promoter activity. While the increase in temperature relieves the inhibition of prfAP1 translation imposed by the prfA thermosensor, prfAP1 translation may still be inhibited via the direct binding of the SreA riboswitch to the 5¢ UTR of prfAP1 transcripts (middle row). Once inside the host cell, PrfA-dependent production of LLO and PlcA mediates the efficient escape of L. monocytogenes from the phagosome into the cytosol, where unknown signals lead to the activation of PrfA and increased expression of prfA from the plcAP promoter. The plcA-prfA transcript results in the accumulation of increased levels of PrfA, which becomes activated via cofactor binding. High levels of activated PrfA increase the expression of a variety of gene products that contribute to L. monocytogenes intracellular replication and cell-to-cell spread (lower row). doi:10.1128/9781555818524.ch19f5

Citation: Xayarath B, Freitag N. 2013. PrfA and the Switch from Environmental Bacterium to Intracellular Pathogen, p 363-385. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch19
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Figure 6

Model depicting the links between carbon transport and metabolism and PrfA-dependent virulence gene expression. The PEP-PTS is a multiprotein phosphorelay system that couples the transport of sugars across the bacterial membrane with their simultaneous phosphorylation. The PTS is comprised of three distinct proteins: EI, histidine protein (Hpr), and the permease EII. (Left) Outside of host cells, L. monocytogenes can be found in environments rich in the presence of PTSdependent sugars, such as the plant sugar cellobiose. Transport of PTS-dependent sugars into the bacterial cell initiates with the autophosphorylation of EI using the phosphoryl group from PEP. EI subsequently transfers a phosphoryl group to Hpr, which then transfers it to the A domain of the EII permease group. As the sugar is transported into the bacterial cell, the phosphoryl group of EIIA is rapidly transferred to the EIIB domain and then to the incoming sugar as it passes through the EIIC domain of the permease. EIIA is therefore in a nonphosphorylated state during active PTS sugar transport, and it is this nonphophorylated form of EIIA that has been proposed to sequester PrfA, thereby reducing or inhibiting its activity. (Right) Within the mammalian cell cytosol, alternative carbon sources such as hexose-phosphate sugars and C3 sugars appear to be the predominant sources of carbohydrates used by L. monocytogenes. Transport of these non-PTS-dependent sugars into the bacterial cell occurs either via facilitated diffusion or through alternative transporters such as the Hpt system. Sugar transport via these alternative pathways leaves the EIIA component of the PTS in its phosphorylated state. It has been proposed that phosphorylated EIIA cannot sequester PrfA, which is then free to bind a cofactor that may be produced either by the bacterial cell or by the host cell. Activated PrfA binds target promoters and induces the expression of multiple bacterial gene products that contribute to host infection. Adapted from Freitag et al., 2009. doi:10.1128/9781555818524.ch19f6

Citation: Xayarath B, Freitag N. 2013. PrfA and the Switch from Environmental Bacterium to Intracellular Pathogen, p 363-385. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch19
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1. Alonzo, F., III,, L. D. Bobo,, D. J. Skiest,, and N. E. Freitag. 2011a. Evidence for subpopulations of Listeria monocytogenes with enhanced invasion of cardiac cells. J. Med. Microbiol. 60: 423 434.
2. Alonzo, F., III,, P. D. McMullen,, and N. E. Freitag. 2011b. Actin polymerization drives septation of Listeria monocytogenes namA hydrolase mutants, demonstrating host correction of a bacterial defect. Infect. Immun. 79: 1458 1470.
3. Alonzo, F., III,, B. Xayarath,, J. C. Whisstock,, and N. E. Freitag. 2011c. Functional analysis of the Listeria monocytogenes secretion chaperone PrsA2 and its multiple contributions to bacterial virulence. Mol. Microbiol. 80: 1530 1548.
4. Alonzo, F., III,, and N. E. Freitag. 2010. Listeria monocytogenes PrsA2 is required for virulence factor secretion and bacterial viability within the host cell cytosol. Infect. Immun. 78: 4944 4957.
5. Alonzo, F., III,, G. C. Port,, M. Cao,, and N. E. Freitag. 2009. The posttranslocation chaperone PrsA2 contributes to multiple facets of Listeria monocytogenes pathogenesis. Infect. Immun. 77: 2612 2623.
6. Antolin, J.,, A. Gutierrez,, R. Segoviano,, R. Lopez,, and R. Ciguenza. 2008. Endocarditis due to Listeria: description of two cases and review of the literature. Eur. J. Intern. Med. 19: 295 296.
7. Baquero, F.,, and M. Lemonnier. 2009. Generational coexistence and ancestor’s inhibition in bacterial populations. FEMS Microbiol. Rev. 33: 958 967.
8. Barabote, R. D.,, and M. H. Saier, Jr. 2005. Comparative genomic analyses of the bacterial phosphotransferase system. Microbiol. Mol. Biol. Rev. 69: 608 634.
9. Begley, M.,, R. D. Sleator,, C. G. Gahan,, and C. Hill. 2005. Contribution of three bile-associated loci, bsh, pva, and btlB, to gastrointestinal persistence and bile tolerance of Listeria monocytogenes. Infect. Immun. 73: 894 904.
10. Bonazzi, M.,, M. Lecuit,, and P. Cossart. 2009a. Listeria monocytogenes internalin and E-cadherin: from bench to bedside. Cold Spring Harbor Perspect. Biol. 1: a003087.
11. Bonazzi, M.,, M. Lecuit,, and P. Cossart. 2009b. Listeria monocytogenes internalin and E-cadherin: from structure to pathogenesis. Cell. Microbiol. 11: 693 702.
12. Borezee, E.,, E. Pellegrini,, and P. Berche. 2000. OppA of Listeria monocytogenes, an oligopeptide-binding protein required for bacterial growth at low temperature and involved in intracellular survival. Infect. Immun. 68: 7069 7077.
13. Bortolussi, R. 2008. Listeriosis: a primer. Can. Med. Assoc. J. 179: 795 797.
14. Bruno, J. C., Jr.,, and N. E. Freitag. 2010. Constitutive activation of PrfA tilts the balance of Listeria monocytogenes fitness towards life within the host versus environmental survival. PLoS One 5: e15138.
15. Camejo, A.,, C. Buchrieser,, E. Couve,, F. Carvalho,, O. Reis,, P. Ferreira,, S. Sousa,, P. Cossart,, and D. Cabanes. 2009. In vivo transcriptional profiling of Listeria monocytogenes and mutagenesis identify new virulence factors involved in infection. PLoS Pathog. 5: e1000449.
16. Camilli, A.,, L. G. Tilney,, and D. A. Portnoy. 1993. Dual roles of plcA in Listeria monocytogenes pathogenesis. Mol. Microbiol. 8: 143 157.
17. Carroll, S. A.,, T. Hain,, U. Technow,, A. Darji,, P. Pashalidis,, S. W. Joseph,, and T. Chakraborty. 2003. Identification and characterization of a peptidoglycan hydrolase, MurA, of Listeria monocytogenes, a muramidase needed for cell separation. J. Bacteriol. 185: 6801 6808.
18. Centers for Disease Control and Prevention. 1998. Multistate outbreak of listeriosis—United States, 1998. MMWR Morb. Mortal. Wkly. Rep. 47: 10851086.
19. Centers for Disease Control and Prevention. 1999. Update: multistate outbreak of listeriosis—United States, 1998-1999. MMWR Morb. Mortal. Wkly. Rep. 47: 11171118.
20. Centers for Disease Control and Prevention. 2002. Outbreak of listeriosis—northeastern United States, 2002. MMWR Morb. Mortal. Wkly. Rep. 51: 950951.
21. Centers for Disease Control and Prevention. 2004. Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food—selected sites, United States, 2003. MMWR Morb. Mortal. Wkly. Rep. 53: 338343.
22. Chakraborty, T.,, M. Leimeister-Wachter,, E. Domann,, M. Hartl,, W. Goebel,, T. Nichterlein,, and S. Notermans. 1992. Coordinate regulation of virulence genes in Listeria monocytogenes requires the product of the prfA gene. J. Bacteriol. 174: 568 574.
23. Chatterjee, S. S.,, H. Hossain,, S. Otten,, C. Kuenne,, K. Kuchmina,, S. Machata,, E. Domann,, T. Chakraborty,, and T. Hain. 2006. Intracellular gene expression profile of Listeria monocytogenes. Infect. Immun. 74: 1323 1338.
24. Chaturongakul, S.,, S. Raengpradub,, M. Wiedmann,, and K. J. Boor. 2008. Modulation of stress and virulence in Listeria monocytogenes. Trends Microbiol. 16: 388 396.
25. Chaudhuri, S.,, J. C. Bruno,, F. Alonzo III,, B. Xayarath,, N. P. Cianciotto,, and N. E. Freitag. 2010. Contribution of chitinases to Listeria monocytogenes pathogenesis. Appl. Environ. Microbiol. 76: 7302 7305.
26. Cheng, L. W.,, and D. A. Portnoy. 2003. Drosophila S2 cells: an alternative infection model for Listeria monocytogenes. Cell. Microbiol. 5: 875 885.
27. Chiang, C.,, C. Bongiorni,, and M. Perego. 2011. Glucose-dependent activation of Bacillus anthracis toxin gene expression and virulence requires the carbon catabolite protein CcpA. J. Bacteriol. 193: 52 62.
28. Chico-Calero, I.,, M. Suarez,, B. Gonzalez-Zorn,, M. Scortti,, J. Slaghuis,, W. Goebel,, and J. A. Vazquez-Boland. 2002. Hpt, a bacterial homolog of the microsomal glucose- 6-phosphate translocase, mediates rapid intracellular proliferation in Listeria. Proc. Natl. Acad. Sci. USA 99: 431 436.
29. Cossart, P.,, and M. Lecuit. 1998. Interactions of Listeria monocytogenes with mammalian cells during entry and actin-based movement: bacterial factors, cellular ligands and signaling. EMBO J. 17: 3797 3806.
30. Cossart, P.,, and A. Toledo-Arana. 2008. Listeria monocytogenes, a unique model in infection biology: an overview. Microbes Infect. 10: 1041 1050.
31. Czuprynski, C. J. 2005. Listeria monocytogenes: silage, sandwiches and science. Anim. Health Res. Rev. 6: 211 217.
32. Delgado, A. R. 2008. Listeriosis in pregnancy. J. Midwifery Womens Health 53: 255 259.
33. Deutscher, J.,, C. Francke,, and P. W. Postma. 2006. How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria. Microbiol. Mol. Biol. Rev. 70: 939 1031.
34. Dons, L.,, E. Eriksson,, Y. Jin,, M. E. Rottenberg,, K. Kristensson,, C. Larsen,, J. Bresciani,, and J. E. Olsen. 2004. Role of flagellin and the two-component CheA/CheY system of Listeria monocytogenes in host cell invasion and virulence. Infect. Immun. 72: 3237 3244.
35. Drevets, D. A.,, and M. S. Bronze. 2008. Listeria monocytogenes: epidemiology, human disease, and mechanisms of brain invasion. FEMS Immunol. Med. Microbiol. 53: 151 165.
36. Dussurget, O.,, D. Cabanes,, P. Dehoux,, M. Lecuit,, C. Buchrieser,, P. Glaser,, and P. Cossart. 2002. Listeria monocytogenes bile salt hydrolase is a PrfA-regulated virulence factor involved in the intestinal and hepatic phases of listeriosis. Mol. Microbiol. 45: 1095 1106.
37. Eisenreich, W.,, T. Dandekar,, J. Heesemann,, and W. Goebel. 2010. Carbon metabolism of intracellular bacterial pathogens and possible links to virulence. Nat. Rev. Microbiol. 8: 401 412.
38. Eiting, M.,, G. Hageluken,, W. D. Schubert,, and D. W. Heinz. 2005. The mutation G145S in PrfA, a key virulence regulator of Listeria monocytogenes, increases DNA-binding affinity by stabilizing the HTH motif. Mol. Microbiol. 56: 433 446.
39. Engelbrecht, F.,, S. K. Chun,, C. Ochs,, J. Hess,, F. Lottspeich,, W. Goebel,, and Z. Sokolovic. 1996. A new PrfA-regulated gene of Listeria monocytogenes encoding a small, secreted protein which belongs to the family of internalins. Mol. Microbiol. 21: 823 837.
40. Eylert, E.,, J. Schar,, S. Mertins,, R. Stoll,, A. Bacher,, W. Goebel,, and W. Eisenreich. 2008. Carbon metabolism of Listeria monocytogenes growing inside macrophages. Mol. Microbiol. 69: 1008 1017.
41. Farber, J. M.,, and P. I. Peterkin. 1991. Listeria monocytogenes, a food-borne pathogen. Microbiol. Rev. 55: 476 511.
42. Farber, J. M.,, W. H. Ross,, and J. Harwig. 1996. Health risk assessment of Listeria monocytogenes in Canada. Int. J. Food Microbiol. 30: 145 156.
43. Fenlon, D. R. 1985. Wild birds and silage as reservoirs of Listeria in the agricultural environment. J. Appl. Bacteriol. 59: 537 543.
44. Fic, E.,, P. Bonarek,, A. Gorecki,, S. Kedracka-Krok,, J. Mikolajczak,, A. Polit,, M. Tworzydlo,, M. Dziedzicka-Wasylewska,, and Z. Wasylewski. 2009. cAMP receptor protein from escherichia coli as a model of signal transduction in proteins—a review. J. Mol. Microbiol. Biotechnol. 17: 1 11.
45. Forster, B. M.,, A. P. Bitar,, E. R. Slepkov,, K. J. Kota,, H. Sondermann,, and H. Marquis. 2011. The metalloprotease of Listeria monocytogenes is regulated by pH. J. Bacteriol. 193: 5090 5097.
46. Freitag, N. E. 2006. From hot dogs to host cells: how the bacterial pathogen Listeria monocytogenes regulates virulence gene expression. Future Microbiol. 1: 89 101.
47. Freitag, N. E.,, G. C. Port,, and M. D. Miner. 2009. Listeria monocytogenes—from saprophyte to intracellular pathogen. Nat. Rev. Microbiol. 7: 623 628.
48. Freitag, N. E.,, and D. A. Portnoy. 1994. Dual promoters of the Listeria monocytogenes prfA transcriptional activator appear essential in vitro but are redundant in vivo. Mol. Microbiol. 12: 845 853.
49. Freitag, N. E.,, L. Rong,, and D. A. Portnoy. 1993. Regulation of the prfA transcriptional activator of Listeria monocytogenes: multiple promoter elements contribute to intracellular growth and cell-to-cell spread. Infect. Immun. 61: 2537 2544.
50. Gandhi, M.,, and M. L. Chikindas. 2007. Listeria: a foodborne pathogen that knows how to survive. Int. J. Food Microbiol. 113: 1 15.
51. Garges, S.,, and S. Adhya. 1985. Sites of allosteric shift in the structure of the cyclic AMP receptor protein. Cell 41: 745 751.
52. Garges, S.,, and S. Adhya. 1988. Cyclic AMP-induced conformational change of cyclic AMP receptor protein (CRP): intragenic suppressors of cyclic AMP-independent CRP mutations. J. Bacteriol. 170: 1417 1422.
53. Gedde, M. M.,, D. E. Higgins,, L. G. Tilney,, and D. A. Portnoy. 2000. Role of listeriolysin O in cell-to-cell spread of Listeria monocytogenes. Infect. Immun. 68: 999 1003.
54. Gellin, B. G.,, and C. V. Broome. 1989. Listeriosis. JAMA 261: 1313 1320.
55. Gibbons, I. S.,, A. Adesiyun,, N. Seepersadsingh,, and S. Rahaman. 2006. Investigation for possible source(s) of contamination of ready-to-eat meat products with Listeria spp. and other pathogens in a meat processing plant in Trinidad. Food Microbiol. 23: 359 366.
56. Glaser, P.,, L. Frangeul,, C. Buchrieser,, C. Rusniok,, A. Amend,, F. Baquero,, P. Berche,, H. Bloecker,, P. Brandt,, T. Chakraborty,, A. Charbit,, F. Chetouani,, E. Couve,, A. de Daruvar,, P. Dehoux,, E. Domann,, G. Dominguez-Bernal,, E. Duchaud,, L. Durant,, O. Dussurget,, K. D. Entian,, H. Fsihi,, F. Garcia-del Portillo,, P. Garrido,, L. Gautier,, W. Goebel,, N. Gomez-Lopez,, T. Hain,, J. Hauf,, D. Jackson,, L. M. Jones,, U. Kaerst,, J. Kreft,, M. Kuhn,, F. Kunst,, G. Kurapkat,, E. Madueno,, A. Maitournam,, J. M. Vicente,, E. Ng,, H. Nedjari,, G. Nordsiek,, S. Novella,, B. de Pablos,, J. C. Perez-Diaz,, R. Purcell,, B. Remmel,, M. Rose,, T. Schlueter,, N. Simoes,, A. Tierrez,, J. A. Vazquez-Boland,, H. Voss,, J. Wehland,, and P. Cossart. 2001. Comparative genomics of Listeria species. Science 294: 849 852.
57. Goldfine, H.,, C. Knob,, D. Alford,, and J. Bentz. 1997. Membrane permeabilization by Listeria monocytogenes phosphatidylinositol-specific phospholipase C is independent of phospholipid hydrolysis and cooperative with listeriolysin O. Proc. Natl. Acad. Sci. USA 94: 2772.
58. Goldfine, H.,, S. J. Wadsworth,, and N. C. Johnston. 2000. Activation of host phospholipases C and D in macrophages after infection with Listeria monocytogenes. Infect. Immun. 68: 5735 5741.
59. Gorke, B.,, and J. Stulke. 2008. Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat. Rev. Microbiol. 6: 613 624.
60. Gottlieb, S. L.,, E. C. Newbern,, P. M. Griffin,, L. M. Graves,, R. Hoekstra,, N. L. Baker,, S. B. Hunter,, K. G. Holt,, F. Ramsey,, M. Head,, P. Levine,, G. Johnson,, D. Schoonmaker-Bopp,, V. Reddy,, L. Kornstein,, M. Gerwel,, J. Nsubuga,, L. Edwards,, S. Stonecipher,, S. Hurd,, D. Austin,, M. A. Jefferson,, S. D. Young,, K. Hise,, E. D. Chernak,, and J. Sobel. 2006. Multistate outbreak of listeriosis linked to turkey deli meat and subsequent changes in US regulatory policy. Clin. Infect. Dis. 42: 29 36.
61. Goyal, A.,, M. Takaine,, V. Simanis,, and K. Nakano. 2011. Dividing the spoils of growth and the cell cycle: the fission yeast as a model for the study of cytokinesis. Cytoskeleton (Hoboken) 68: 69 88.
62. Gray, M. J.,, N. E. Freitag,, and K. J. Boor. 2006. How the bacterial pathogen Listeria monocytogenes mediates the switch from environmental Dr. Jekyll to pathogenic Mr. Hyde. Infect. Immun. 74: 2505 2512.
63. Gray, M. L.,, and A. H. Killinger. 1966. Listeria monocytogenes and listeric infections. Bacteriol. Rev. 30: 309 382.
64. Guinane, C. M.,, P. D. Cotter,, R. P. Ross,, and C. Hill. 2006. Contribution of penicillin-binding protein homologs to antibiotic resistance, cell morphology, and virulence of Listeria monocytogenes EGDe. Antimicrob. Agents Chemother. 50: 2824 2828.
65. Hardy, J.,, P. Chu,, and C. H. Contag. 2009. Foci of Listeria monocytogenes persist in the bone marrow. Dis. Model Mech. 2: 39 46.
66. Hardy, J.,, K. P. Francis,, M. DeBoer,, P. Chu,, K. Gibbs,, and C. H. Contag. 2004. Extracellular replication of Listeria monocytogenes in the murine gall bladder. Science 303: 851 853.
67. Harman, J. G.,, M. McKenney,, and A. Peterkofsky. 1986. Structure-function analysis of three cAMP-independent forms of the cAMP receptor protein. J. Biol. Chem. 261: 16332 16339.
68. Herler, M.,, A. Bubert,, M. Goetz,, Y. Vega,, J. A. Vazquez-Boland,, and W. Goebel. 2001. Positive selection of mutations leading to loss or reduction of transcriptional activity of PrfA, the central regulator of Listeria monocytogenes virulence. J. Bacteriol. 183: 5562 5570.
69. Ireton, K. 2007. Entry of the bacterial pathogen Listeria monocytogenes into mammalian cells. Cell. Microbiol. 9: 1365 1375.
70. Ireton, K.,, and P. Cossart. 1997. Host-pathogen interactions during entry and actin-based movement of Listeria monocytogenes. Annu. Rev. Genet. 31: 113 138.
71. Jensen, V. B.,, J. T. Harty,, and B. D. Jones. 1998. Interactions of the invasive pathogens Salmonella typhimurium, Listeria monocytogenes, and Shigella flexneri with M cells and murine Peyer’s patches. Infect. Immun. 66: 3758 3766.
72. Johansson, J.,, P. Mandin,, A. Renzoni,, C. Chiaruttini,, M. Springer,, and P. Cossart. 2002. An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110: 551 561.
73. Joseph, B.,, and W. Goebel. 2007. Life of Listeria monocytogenes in the host cells’ cytosol. Microbes Infect. 9: 1188 1195.
74. Joseph, B.,, S. Mertins,, R. Stoll,, J. Schar,, K. R. Umesha,, Q. Luo,, S. Muller-Altrock,, and W. Goebel. 2008. Glycerol metabolism and PrfA activity in Listeria monocytogenes. J. Bacteriol. 190: 5412 5430.
75. Joseph, B.,, K. Przybilla,, C. Stuhler,, K. Schauer,, J. Slaghuis,, T. M. Fuchs,, and W. Goebel. 2006. Identification of Listeria monocytogenes genes contributing to intracellular replication by expression profiling and mutant screening. J. Bacteriol. 188: 556 568.
76. Kaiser, D. 2008. Myxococcus—from single-cell polarity to complex multicellular patterns. Annu. Rev. Genet. 42: 109 130.
77. Keeney, K.,, L. Colosi,, W. Weber,, and M. O’Riordan. 2009. Generation of branched-chain fatty acids through lipoate-dependent metabolism facilitates intracellular growth of Listeria monocytogenes. J. Bacteriol. 191: 2187 2196.
78. Keeney, K. M.,, J. A. Stuckey,, and M. X. O’Riordan. 2007. LplA1-dependent utilization of host lipoyl peptides enables Listeria cytosolic growth and virulence. Mol. Microbiol. 66: 758 770.
79. Kim, H.,, K. J. Boor,, and H. Marquis. 2004. Listeria monocytogenes σ B contributes to invasion of human intestinal epithelial cells. Infect. Immun. 72: 7374 7378.
80. Kim, H.,, H. Marquis,, and K. J. Boor. 2005. σ B contributes to Listeria monocytogenes invasion by controlling expression of inlA and inlB. Microbiology 151: 3215 3222.
81. Kim, J.,, S. Adhya,, and S. Garges. 1992. Allosteric changes in the cAMP receptor protein of Escherichia coli: hinge reorientation. Proc. Natl. Acad. Sci. USA 89: 9700 9704.
82. Kocks, C.,, E. Gouin,, M. Tabouret,, P. Berche,, H. Ohayon,, and P. Cossart. 1992. L. monocytogenes-induced actin assembly requires the actA gene product, a surface protein. Cell 68: 521 531.
83. Kocks, C.,, R. Hellio,, P. Gounon,, H. Ohayon,, and P. Cossart. 1993. Polarized distribution of Listeria monocytogenes surface protein ActA at the site of directional actin assembly. J. Cell Sci. 05( Pt. 3): 699 710.
84. Korner, H.,, H. J. Sofia,, and W. G. Zumft. 2003. Phylogeny of the bacterial superfamily of Crp-Fnr transcription regulators: exploiting the metabolic spectrum by controlling alternative gene programs. FEMS Microbiol. Rev. 27: 559 592.
85. Kreft, J.,, and J. A. Vazquez-Boland. 2001. Regulation of virulence genes in Listeria. Int. J. Med. Microbiol. 291: 145 157.
86. Kreft, J.,, J. A. Vazquez-Boland,, S. Altrock,, G. Dominguez-Bernal,, and W. Goebel. 2002. Pathogenicity islands and other virulence elements in Listeria. Curr. Top. Microbiol. Immunol. 264: 109 125.
87. Lambrechts, A.,, K. Gevaert,, P. Cossart,, J. Vandekerckhove,, and M. Van Troys. 2008. Listeria comet tails: the actin-based motility machinery at work. Trends Cell Biol. 18: 220 227.
88. Larsen, M. H.,, J. J. Leisner,, and H. Ingmer. 2010. The chitinolytic activity of Listeria monocytogenes EGD is regulated by carbohydrates but also by the virulence regulator PrfA. Appl. Environ. Microbiol. 76: 6470 6476.
89. Lecuit, M. 2007. Human listeriosis and animal models. Microbes Infect. 9: 1216 1225.
90. Lecuit, M.,, S. Vandormael-Pournin,, J. Lefort,, M. Huerre,, P. Gounon,, C. Dupuy,, C. Babinet,, and P. Cossart. 2001. A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier. Science 292: 1722 1725.
91. Lingnau, A.,, E. Domann,, M. Hudel,, M. Bock,, T. Nichterlein,, J. Wehland,, and T. Chakraborty. 1995. Expression of the Listeria monocytogenes EGD inlA and inlB genes, whose products mediate bacterial entry into tissue culture cell lines, by PrfA-dependent and -independent mechanisms. Infect. Immun. 63: 3896 3903.
92. Loh, E.,, O. Dussurget,, J. Gripenland,, K. Vaitkevicius,, T. Tiensuu,, P. Mandin,, F. Repoila,, C. Buchrieser,, P. Cossart,, and J. Johansson. 2009. A trans-acting riboswitch controls expression of the virulence regulator PrfA in Listeria monocytogenes. Cell 139: 770 779.
93. Luo, Q.,, M. Rauch,, A. K. Marr,, S. Muller-Altrock,, and W. Goebel. 2004. In vitro transcription of the Listeria monocytogenes virulence genes inlC and mpl reveals overlapping PrfA-dependent and -independent promoters that are differentially activated by GTP. Mol. Microbiol. 52: 39 52.
94. Lynch, M.,, J. Painter,, R. Woodruff,, and C. Braden. 2006. Surveillance for foodborne-disease outbreaks—United States, 1998-2002. MMWR Surveill. Summ. 55: 1 42.
95. MacGowan, A. P.,, P. H. Cartlidge,, F. MacLeod,, and J. McLaughlin. 1991. Maternal listeriosis in pregnancy without fetal or neonatal infection. J. Infect. 22: 53 57.
96. Mansfield, B. E.,, M. S. Dionne,, D. S. Schneider,, and N. E. Freitag. 2003. Exploration of host-pathogen interactions using Listeria monocytogenes and Drosophila melanogaster. Cell. Microbiol. 5: 901 911.
97. Marquis, H.,, H. G. Bouwer,, D. J. Hinrichs,, and D. A. Portnoy. 1993. Intracytoplasmic growth and virulence of Listeria monocytogenes auxotrophic mutants. Infect. Immun. 61: 3756 3760.
98. Marquis, H.,, V. Doshi,, and D. A. Portnoy. 1995. The broad-range phospholipase C and a metalloprotease mediate listeriolysin O-independent escape of Listeria monocytogenes from a primary vacuole in human epithelial cells. Infect. Immun. 63: 4531 4534.
99. Marquis, H.,, and E. J. Hager. 2000. pH-regulated activation and release of a bacteria-associated phospholipase C during intracellular infection by Listeria monocytogenes. Mol. Microbiol. 35: 289 298.
100. Marr, A. K.,, B. Joseph,, S. Mertins,, R. Ecke,, S. Muller-Altrock,, and W. Goebel. 2006. Overexpression of PrfA leads to growth inhibition of Listeria monocytogenes in glucose-containing culture media by interfering with glucose uptake. J. Bacteriol. 188: 3887 3901.
101. McClure, E. M.,, and R. L. Goldenberg. 2009. Infection and stillbirth. Semin. Fetal Neonatal Med. 14: 182 189.
102. McGann, P.,, S. Raengpradub,, R. Ivanek,, M. Wiedmann,, and K. J. Boor. 2008. Differential regulation of Listeria monocytogenes internalin and internalin-like genes by σ B and PrfA as revealed by subgenomic microarray analyses. Foodborne Pathog. Dis. 5: 417 435.
103. McGann, P.,, M. Wiedmann,, and K. J. Boor. 2007. The alternative sigma factor sigma B and the virulence gene regulator PrfA both regulate transcription of Listeria monocytogenes internalins. Appl. Environ. Microbiol. 73: 2919 2930.
104. Mead, P. S.,, E. F. Dunne,, L. Graves,, M. Wiedmann,, M. Patrick,, S. Hunter,, E. Salehi,, F. Mostashari,, A. Craig,, P. Mshar,, T. Bannerman,, B. D. Sauders,, P. Hayes,, W. Dewitt,, P. Sparling,, P. Griffin,, D. Morse,, L. Slutsker,, and B. Swaminathan. 2006. Nationwide outbreak of listeriosis due to contaminated meat. Epidemiol. Infect. 134: 744 751.
105. Meisch, F.,, and M. N. Prioleau. 2011. Genomic approaches to the initiation of DNA replication and chromatin structure reveal a complex relationship. Brief Funct. Genomics 10: 30 36.
106. Mengaud, J.,, S. Dramsi,, E. Gouin,, J. A. Vazquez-Boland,, G. Milon,, and P. Cossart. 1991. Pleiotropic control of Listeria monocytogenes virulence factors by a gene that is autoregulated. Mol. Microbiol. 5: 2273 2283.
107. Mengaud, J.,, M. F. Vicente,, and P. Cossart. 1989. Transcriptional mapping and nucleotide sequence of the Listeria monocytogenes hlyA region reveal structural features that may be involved in regulation. Infect. Immun. 57: 3695 3701.
108. Mertins, S.,, B. Joseph,, M. Goetz,, R. Ecke,, G. Seidel,, M. Sprehe,, W. Hillen,, W. Goebel,, and S. Muller-Altrock. 2007. Interference of components of the phosphoenolpyruvate phosphotransferase system with the central virulence gene regulator PrfA of Listeria monocytogenes. J. Bacteriol. 189: 473 490.
109. Milenbachs, A. A.,, D. P. Brown,, M. Moors,, and P. Youngman. 1997. Carbon-source regulation of virulence gene expression in Listeria monocytogenes. Mol. Microbiol. 23: 1075 1085.
110. Milenbachs Lukowiak, A.,, K. J. Mueller,, N. E. Freitag,, and P. Youngman. 2004. Deregulation of Listeria monocytogenes virulence gene expression by two distinct and semi-independent pathways. Microbiology 150: 321 333.
111. Milohanic, E.,, P. Glaser,, J. Y. Coppee,, L. Frangeul,, Y. Vega,, J. A. Vazquez-Boland,, F. Kunst,, P. Cossart,, and C. Buchrieser. 2003. Transcriptome analysis of Listeria monocytogenes identifies three groups of genes differently regulated by PrfA. Mol. Microbiol. 47: 1613 1625.
112. Miner, M. D.,, G. C. Port,, H. G. Bouwer,, J. C. Chang,, and N. E. Freitag. 2008a. A novel prfA mutation that promotes Listeria monocytogenes cytosol entry but reduces bacterial spread and cytotoxicity. Microb. Pathog. 45: 273 281.
113. Miner, M. D.,, G. C. Port,, and N. E. Freitag. 2008b. Functional impact of mutational activation on the Listeria monocytogenes central virulence regulator PrfA. Microbiology 154: 3579 3589.
114. Monk, I. R.,, C. G. Gahan,, and C. Hill. 2008. Tools for functional postgenomic analysis of Listeria monocytogenes. Appl. Environ. Microbiol. 74: 3921 3934.
115. Moran, C. P., 1993. RNA polymerase and transcription factors, p. 653 657. In A. L. Sonenshein,, J. A. Hoch,, and R. Losick (ed.), Bacillus subtilis and Other Gram-Positive Bacteria: Biochemistry, Physiology, and Molecular Genetics. American Society for Microbiology, Washington, DC.
116. Mueller, K. J.,, and N. E. Freitag. 2005. Pleiotropic enhancement of bacterial pathogenesis resulting from the constitutive activation of the Listeria monocytogenes regulatory factor PrfA. Infect. Immun. 73: 1917 1926.
117. Nair, S.,, E. Milohanic,, and P. Berche. 2000. ClpC ATPase is required for cell adhesion and invasion of Listeria monocytogenes. Infect. Immun. 68: 7061 7068.
118. Ollinger, J.,, M. Wiedmann,, and K. J. Boor. 2008. σ B- and PrfA-dependent transcription of genes previously classified as putative constituents of the Listeria monocytogenes PrfA regulon. Foodborne Pathog. Dis. 5: 281 293.
119. O’Neil, H. S.,, and H. Marquis. 2006. Listeria monocytogenes flagella are used for motility, not as adhesins, to increase host cell invasion. Infect. Immun. 74: 6675 6681.
120. Park, S. F.,, and R. G. Kroll. 1993. Expression of listeriolysin and phosphatidylinositol-specific phospholipase C is repressed by the plant-derived molecule cellobiose in Listeria monocytogenes. Mol. Microbiol. 8: 653 661.
121. Pizarro-Cerda, J.,, and P. Cossart. 2006. Subversion of cellular functions by Listeria monocytogenes. J. Pathol. 208: 215 223.
122. Port, G. C.,, and N. E. Freitag. 2007. Identification of novel Listeria monocytogenes secreted virulence factors following mutational activation of the central virulence regulator, PrfA. Infect. Immun. 75: 5886 5897.
123. Portnoy, D. A.,, P. S. Jacks,, and D. J. Hinrichs. 1988. Role of hemolysin for the intracellular growth of Listeria monocytogenes. J. Exp. Med. 167: 1459 1471.
124. Portnoy, D. A.,, and S. Jones. 1994. The cell biology of Listeria monocytogenes infection (escape from a vacuole). Ann. N. Y. Acad. Sci. 730: 15 25.
125. Poyart, C.,, E. Abachin,, I. Razafimanantsoa,, and P. Berche. 1993. The zinc metalloprotease of Listeria monocytogenes is required for maturation of phosphatidylcholine phospholipase C: direct evidence obtained by gene complementation. Infect. Immun. 61: 1576 1580.
126. Quillin, S. J.,, K. T. Schwartz,, and J. H. Leber. 2011. The novel Listeria monocytogenes bile sensor BrtA controls expression of the cholic acid efflux pump MdrT. Mol. Microbiol. 81: 129 142.
127. Rae, C. S.,, A. Geissler,, P. C. Adamson,, and D. A. Portnoy. 2011. Mutations of the Listeria monocytogenes peptidoglycan N-deacetylase and O-acetylase result in enhanced lysozyme sensitivity, bacteriolysis, and hyperinduction of innate immune pathways. Infect. Immun. 79: 3596 3606.
128. Rajabian, T.,, B. Gavicherla,, M. Heisig,, S. Muller-Altrock,, W. Goebel,, S. D. Gray-Owen,, and K. Ireton. 2009. The bacterial virulence factor InlC perturbs apical cell junctions and promotes cell-to-cell spread of Listeria. Nat. Cell Biol. 11: 1212 1218.
129. Ramaswamy, V.,, V. M. Cresence,, J. S. Rejitha,, M. U. Lekshmi,, K. S. Dharsana,, S. P. Prasad,, and H. M. Vijila. 2007. Listeria—review of epidemiology and pathogenesis. J. Microbiol. Immunol. Infect. 40: 4 13.
130. Rauch, M.,, Q. Luo,, S. Muller-Altrock,, and W. Goebel. 2005. SigB-dependent in vitro transcription of prfA and some newly identified genes of Listeria monocytogenes whose expression is affected by PrfA in vivo. J. Bacteriol. 187: 800 804.
131. Raveneau, J.,, C. Geoffroy,, J. L. Beretti,, J. L. Gaillard,, J. E. Alouf,, and P. Berche. 1992. Reduced virulence of a Listeria monocytogenes phospholipase-deficient mutant obtained by transposon insertion into the zinc metalloprotease gene. Infect. Immun. 60: 916 921.
132. Renzoni, A.,, A. Klarsfeld,, S. Dramsi,, and P. Cossart. 1997. Evidence that PrfA, the pleiotropic activator of virulence genes in Listeria monocytogenes, can be present but inactive. Infect. Immun. 65: 1515 1518.
133. Ripio, M. T.,, K. Brehm,, M. Lara,, M. Suarez,, and J. A. Vazquez-Boland. 1997a. Glucose-1-phosphate utilization by Listeria monocytogenes is PrfA dependent and coordinately expressed with virulence factors. J. Bacteriol. 179: 7174 7180.
134. Ripio, M. T.,, G. Dominguez-Bernal,, M. Lara,, M. Suarez,, and J. A.Vazquez-Boland. 1997b. A Gly145Ser substitution in the transcriptional activator PrfA causes constitutive overexpression of virulence factors in Listeria monocytogenes. J. Bacteriol. 179: 1533 1540.
135. Sanderson, S.,, D. J. Campbell,, and N. Shastri. 1995. Identification of a CD4+ T cell-stimulating antigen of pathogenic bacteria by expression cloning. J. Exp. Med. 182: 1751 1757.
136. Schlech, W. F., III,, P. M. Lavigne,, R. A. Bortolussi,, A. C. Allen,, E. V. Haldane,, A. J. Wort,, A. W. Hightower,, S. E. Johnson,, S. H. King,, E. S. Nicholls,, and C. V. Broome. 1983. Epidemic listeriosis—evidence for transmission by food. N. Engl. J. Med. 308: 203 206.
137. Schnupf, P.,, and D. A. Portnoy. 2007. Listeriolysin O: a phagosome-specific lysin. Microbes Infect. 9: 1176 1187.
138. Schwartz, B.,, C. A. Ciesielski,, C. V. Broome,, S. Gaventa,, G. R. Brown,, B. G. Gellin,, A. W. Hightower,, and L. Mascola. 1988. Association of sporadic listeriosis with consumption of uncooked hot dogs and undercooked chicken. Lancet 2: 779 782.
139. Scortti, M.,, H. J. Monzo,, L. Lacharme-Lora,, D. A. Lewis,, and J. A. Vazquez-Boland. 2007. The PrfA virulence regulon. Microbes Infect. 9: 1196 1207.
140. Seveau, S.,, J. Pizarro-Cerda,, and P. Cossart. 2007. Molecular mechanisms exploited by Listeria monocytogenes during host cell invasion. Microbes Infect. 9: 1167 1175.
141. Shen, A.,, and D. E. Higgins. 2005. The 5' untranslated region-mediated enhancement of intracellular listeriolysin O production is required for Listeria monocytogenes pathogenicity. Mol. Microbiol. 57: 1460 1473.
142. Shetron-Rama, L. M.,, K. Mueller,, J. M. Bravo,, H. G. Bouwer,, S. S. Way,, and N. E. Freitag. 2003. Isolation of Listeria monocytogenes mutants with high-level in vitro expression of host cytosol-induced gene products. Mol. Microbiol. 48: 1537 1551.
143. Sleator, R. D.,, H. H. Wemekamp-Kamphuis,, C. G. Gahan,, T. Abee,, and C. Hill. 2005. A PrfA-regulated bile exclusion system (BilE) is a novel virulence factor in Listeria monocytogenes. Mol. Microbiol. 55: 1183 1195.
144. Smith, G. A.,, H. Marquis,, S. Jones,, N. C. Johnston,, D. A. Portnoy,, and H. Goldfine. 1995. The two distinct phospholipases C of Listeria monocytogenes have overlapping roles in escape from a vacuole and cell-to-cell spread. Infect. Immun. 63: 4231 4237.
145. Stack, H. M.,, R. D. Sleator,, M. Bowers,, C. Hill,, and C. G. Gahan. 2005. Role for HtrA in stress induction and virulence potential in Listeria monocytogenes. Appl. Environ. Microbiol. 71: 4241 4247.
146. Stavru, F.,, C. Archambaud,, and P. Cossart. 2011. Cell biology and immunology of Listeria monocytogenes infections: novel insights. Immunol. Rev. 240: 160 184.
147. Stoll, R.,, S. Mertins,, B. Joseph,, S. Muller-Altrock,, and W. Goebel. 2008. Modulation of PrfA activity in Listeria monocytogenes upon growth in different culture media. Microbiology 154: 3856 3876.
148. Stone, S. C.,, and J. Shoenberger. 2001. Update: multistate outbreak of listeriosis—United States, 2000. Ann. Emerg. Med. 38: 339 341.
149. Swaminathan, B.,, and P. Gerner-Smidt. 2007. The epidemiology of human listeriosis. Microbes Infect. 9: 1236 1243.
150. Swaminathan, B.,, P. Gerner-Smidt,, and J. M. Whichard. 2006. Foodborne disease trends and reports. Foodborne Pathog. Dis. 3: 316 318.
151. Tilney, L. G.,, P. S. Connelly,, and D. A. Portnoy. 1990. Actin filament nucleation by the bacterial pathogen, Listeria monocytogenes. J. Cell Biol. 111: 2979 2988.
152. Tilney, L. G.,, and D. A. Portnoy. 1989. Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes. J. Cell Biol. 109: 1597 1608.
153. Toledo-Arana, A.,, O. Dussurget,, G. Nikitas,, N. Sesto,, H. Guet-Revillet,, D. Balestrino,, E. Loh,, J. Gripenland,, T. Tiensuu,, K. Vaitkevicius,, M. Barthelemy,, M. Vergassola,, M. A. Nahori,, G. Soubigou,, B. Regnault,, J. Y. Coppee,, M. Lecuit,, J. Johansson,, and P. Cossart. 2009. The Listeria transcriptional landscape from saprophytism to virulence. Nature 459: 950 956.
154. Tsvetanova, B.,, A. C. Wilson,, C. Bongiorni,, C. Chiang,, J. A. Hoch,, and M. Perego. 2007. Opposing effects of histidine phosphorylation regulate the AtxA virulence transcription factor in Bacillus anthracis. Mol. Microbiol. 63: 644 655.
155. Vazquez-Boland, J. A.,, C. Kocks,, S. Dramsi,, H. Ohayon,, C. Geoffroy,, J. Mengaud,, and P. Cossart. 1992. Nucleotide sequence of the lecithinase operon of Listeria monocytogenes and possible role of lecithinase in cell-to-cell spread. Infect. Immun. 60: 219 230.
156. Vazquez-Boland, J. A.,, M. Kuhn,, P. Berche,, T. Chakraborty,, G. Dominguez-Bernal,, W. Goebel,, B. Gonzalez-Zorn,, J. Wehland,, and J. Kreft. 2001. Listeria pathogenesis and molecular virulence determinants. Clin. Microbiol. Rev. 14: 584 640.
157. Vega, Y.,, C. Dickneite,, M. T. Ripio,, R. Bockmann,, B. Gonzalez-Zorn,, S. Novella,, G. Dominguez-Bernal,, W. Goebel,, and J. A. Vazquez-Boland. 1998. Functional similarities between the Listeria monocytogenes virulence regulator PrfA and cyclic AMP receptor protein: the PrfA* (Gly145Ser) mutation increases binding affinity for target DNA. J. Bacteriol. 180: 6655 6660.
158. Vega, Y.,, M. Rauch,, M. J. Banfield,, S. Ermolaeva,, M. Scortti,, W. Goebel,, and J. A. Vazquez-Boland. 2004. New Listeria monocytogenes prfA* mutants, transcriptional properties of PrfA* proteins and structure-function of the virulence regulator PrfA. Mol. Microbiol. 52: 1553 1565.
159. Wadsworth, S. J.,, and H. Goldfine. 1999. Listeria monocytogenes phospholipase C-dependent calcium signaling modulates bacterial entry into J774 macrophage-like cells. Infect. Immun. 67: 1770 1778.
160. Waters, L. S.,, and G. Storz. 2009. Regulatory RNAs in bacteria. Cell 136: 615 628.
161. Way, S. S.,, L. J. Thompson,, J. E. Lopes,, A. M. Hajjar,, T. R. Kollmann,, N. E. Freitag,, and C. B. Wilson. 2004. Characterization of flagellin expression and its role in Listeria monocytogenes infection and immunity. Cell. Microbiol. 6: 235 242.
162. Williams, J. R.,, C. Thayyullathil,, and N. E. Freitag. 2000. Sequence variations within PrfA DNA binding sites and effects on Listeria monocytogenes virulence gene expression. J. Bacteriol. 182: 837 841.
163. Wilson, R. L.,, L. L. Brown,, D. Kirkwood-Watts,, T. K. Warren,, S. A. Lund,, D. S. King,, K. F. Jones,, and D. E. Hruby. 2006. Listeria monocytogenes 10403S HtrA is necessary for resistance to cellular stress and virulence. Infect. Immun. 74: 765 768.
164. Winkler, W. C.,, and R. R. Breaker. 2005. Regulation of bacterial gene expression by riboswitches. Annu. Rev. Microbiol. 59: 487 517.
165. Wong, K. K.,, H. G. Bouwer,, and N. E. Freitag. 2004. Evidence implicating the 5' untranslated region of Listeria monocytogenes actA in the regulation of bacterial actin-based motility. Cell. Microbiol. 6: 155 166.
166. Wong, K. K.,, and N. E. Freitag. 2004. A novel mutation within the central Listeria monocytogenes regulator PrfA that results in constitutive expression of virulence gene products. J. Bacteriol. 186: 6265 6276.
167. Xayarath, B.,, H. Marquis,, G. C. Port,, and N. E. Freitag. 2009. Listeria monocytogenes CtaP is a multifunctional cysteine transport-associated protein required for bacterial pathogenesis. Mol. Microbiol. 74: 956 973.
168. Xayarath, B.,, J. I. Smart,, K. J. Mueller,, and N. E. Freitag. 2011a. A novel C-terminal mutation resulting in constitutive activation of the Listeria monocytogenes central virulence regulatory factor PrfA. Microbiology 157( Pt. 11): 3138 3149.
169. Xayarath, B.,, K. W. Volz,, J. I. Smart,, and N. E. Freitag. 2011b. Probing the role of protein surface charge in the activation of PrfA, the central regulator of Listeria monocytogenes pathogenesis. PLoS One 6: e23502.
170. Yeung, P. S.,, Y. Na,, A. J. Kreuder,, and H. Marquis. 2007. Compartmentalization of the broad-range phospholipase C activity to the spreading vacuole is critical for Listeria monocytogenes virulence. Infect. Immun. 75: 44 51.
171. Yeung, P. S.,, N. Zagorski,, and H. Marquis. 2005. The metalloprotease of Listeria monocytogenes controls cell wall translocation of the broad-range phospholipase C. J. Bacteriol. 187: 2601 2608.
172. Youn, H.,, R. L. Kerby,, M. Conrad,, and G. P. Roberts. 2006. Study of highly constitutively active mutants suggests how cAMP activates cAMP receptor protein. J. Biol. Chem. 281: 1119 1127.


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Table 1

Gene products directly or indirectly regulated by PrfA

Citation: Xayarath B, Freitag N. 2013. PrfA and the Switch from Environmental Bacterium to Intracellular Pathogen, p 363-385. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch19

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