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Chapter 52 : Regulation of Virulence Genes in Pathogenic Listeria spp.

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Abstract:

Regulation of virulence genes in pathogenic bacteria must occur by mechanisms allowing the coordinate and differential expression of the virulence factors during infection. Although positive regulatory factor A (PrfA) and (to some extent) sigma factor B (SigB), are not specific for the pathogenic species, they have been so far shown by genetic and biochemical studies to be involved in the regulation of virulence genes. This chapter focuses on gene regulation by PrfA. Extensive molecular studies have been carried out with the cyclic AMP (cAMP)-binding factor Crp; since PrfA shares extended sequential and structural similarity with Crp, a short overview of the most essential features of Crp has been provided in this chapter for the understanding of PrfA. The three-dimensional structure of PrfA shows high structural similarity with Crp. The chapter discusses some evidence for the involvement of a low-molecular-weight effector(s) for PrfA that is distinct from cAMP. The results described in the chapter suggest that regulation of virulence genes mediated by PrfA involves environmental parameters, as well as additional bacterial factors. The transcriptional activator of the pathogenic species and shares common properties with other members of the Crp/Fnr family to which it belongs, but it also possesses unique features. The precise knowledge of the mechanisms involved in the regulation of the listerial virulence genes will be crucial for the understanding of the pathogenesis of infections by pathogenic spp.

Citation: Goebel W, Müller-Altrock S, Kreft J. 2006. Regulation of Virulence Genes in Pathogenic Listeria spp., p 634-645. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch52

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FIGURE 1

(A) Comparison of the amino acid sequences of the PrfA proteins from , , and . The pound sign (#) indicates conserved glycines at the turns of the β-roll structure; an asterisk (*) indicates the position of the G145S substitution, leading to a constitutively active PrfA ( ). Sequences are from references , and . (B) Structure and transcriptional orga-nization of the PrfA-dependent virulence gene cluster (LIPI-1) and of other PrfA-dependent virulence genes in and . Genes and products: , phosphoribosyl synthase; , positive regulatory factor A; , phosphatidylinositol-specific phospholipase C; , listeriolysin O; , metalloprotease; , actin-polymerization protein; , broad-range phospholipase C (lecithinase); orfXYZ and orfBA, open reading frames of unknown function; , lactate dehydrogenase; and , large cell-wall-bound internalins A and B; , small secreted internalin C; , hexose phosphate transporter; , bile acid hydrolase; P, promoter. An asterisk above indicates the presence of a PrfA box within the promoter. Thin arrows above the gene symbols indicate the different transcripts. Arrows below with a plus or minus sign indicate transcriptional induction or repression, respectively, by PrfA. Filled pentagons show the additional open reading frames present in LIPI-1 of .

Citation: Goebel W, Müller-Altrock S, Kreft J. 2006. Regulation of Virulence Genes in Pathogenic Listeria spp., p 634-645. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch52
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Image of FIGURE 2
FIGURE 2

(A) Schematic comparison of Crp from ( ) and PrfA from . The functionally important features of Crp (e.g., the N-terminal β-roll structures, the C-terminal HTH motif, and the activating regions AR1, AR2, and AR3) are indicated, as well as amino acids known to be involved in cAMP and DNA binding. Capital letters (A to D) denote alpha-helical regions. For PrfA, the predicted N-terminal HTH motif and the putative leucine zipper (Leu-zip) structure are marked. Amino acid replacements in PrfA that cause a decreased (−) or increased (+) level of activity are shown above. (B) Three-dimensional structures of Crp ( ) and PrfA ( ).

Citation: Goebel W, Müller-Altrock S, Kreft J. 2006. Regulation of Virulence Genes in Pathogenic Listeria spp., p 634-645. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch52
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Image of FIGURE 3
FIGURE 3

Sequence comparison of PrfA-regulated virulence gene promoters from and . Sequences are from published data or from our own unpublished results.

Citation: Goebel W, Müller-Altrock S, Kreft J. 2006. Regulation of Virulence Genes in Pathogenic Listeria spp., p 634-645. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch52
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Tables

Generic image for table
Table 1

Regulators specific for Listeria monocytogenes EGD-e

Sequences are from ListiList (http://genolist.pasteur.fr/ListiList/) ( ).

Citation: Goebel W, Müller-Altrock S, Kreft J. 2006. Regulation of Virulence Genes in Pathogenic Listeria spp., p 634-645. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch52

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