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Chapter 14 : What Genomics Has Taught Us about Intracellular Pathogens: the Example of

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Abstract:

This chapter discusses the insights gained from genomics of intracellular pathogens using as an example. The genus comprises six species, two of which are pathogenic, for humans and animals, and , mainly for ruminants. is an environmental bacterium that lives on decomposing plants, but the acquisition of virulence factors, most probably by horizontal gene transfer, allows to also infect humans and many other mammalian hosts. The newly studied surface proteins are present in all strains investigated. Further studies should focus on strain-specific surface proteins because diversity among these may account for strain differences in virulence and in niche adaptation. Williams and colleagues introduced in-frame deletions into 15 of 16 response regulator genes and characterized the resulting mutants. In this study, the deletion of the individual response regulator genes had only minor effects on in vitro and in vivo growth of the bacteria, except for DegU. A coupled bioinformatics/microarray approach applied to identify sigma B-regulated genes confirmed the overlap between the PrfA and the sigma B regulon. In this study, SigB-dependent promoter sequences were searched in the EGDe genome sequence. The pronounced diversity among LPXTG proteins, identified by whole-genome comparisons, was further substantiated by this comparative genomics study using DNA/DNA array hybridization.

Citation: Buchrieser C, Cossart P. 2007. What Genomics Has Taught Us about Intracellular Pathogens: the Example of , p 361-391. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch14
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FIGURE 1

Schematic representation of the infection cycle of . The successive steps are: entry ( ), lysis of the vacuole ( ), intracellular replication ( ), intracellular movements ( ), cell-to-cell spread ( ), formation, and lysis ( ) of two-membrane vacuole. Virulence factors involved at the different steps are indicated (from reference ).

Citation: Buchrieser C, Cossart P. 2007. What Genomics Has Taught Us about Intracellular Pathogens: the Example of , p 361-391. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch14
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Image of FIGURE 2
FIGURE 2

genetic diversity. Gray and black denote presence and absence of genes, respectively. (A) The dendrogram shows estimates of genomic relationships of the 113 strains constructed by hierarchical cluster analysis with the program J-Express. Phylogenetic lineages and subgroups are indicated. (B) Enlargements represent the blocs of lineage-specific genes whose numbers are indicated on the right-hand side. I: lineage I (serovars 1/2a; 1/2c, 3a, 3c); II: lineage II (serovars 4b, 4d, 4e,1/2b, 3b); III: lineage III (serovars 4a, 4c); I.1: serovars 1/2a, 3a; I.2: serovars 1/2c, 3c; II.1: serovars 4b, 4d, 4e; II.2: serovars 1/2b, 3b.

Citation: Buchrieser C, Cossart P. 2007. What Genomics Has Taught Us about Intracellular Pathogens: the Example of , p 361-391. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch14
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Image of FIGURE 3
FIGURE 3

Schematic presentation of the virulence gene cluster in and its comparison with the orthologous region in . Orthologous genes among the different sp. are depicted in the same color or shading pattern. The gene cluster is flanked by the housekeeping genes (light blue arrows) and in all six species of and are also present in . Known virulence genes de facto or potentially regulated by PrfA are depicted in red (freely adapted from references , and ).

Citation: Buchrieser C, Cossart P. 2007. What Genomics Has Taught Us about Intracellular Pathogens: the Example of , p 361-391. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch14
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Image of FIGURE 4
FIGURE 4

Schematic presentation of the locus and the flanking regions of and and its hypothetical ancestral organization. EGD, F6854, CLIP80459, F2365, H7858: strain designations. Clip 11262: strain designation. Orthologous genes are depicted in the same shading pattern. Black indicates locus; dotted lines, specific regions with respect to the other genomes; , gene names of EGDe, , gene names of CLIP80459, , gene names of F2365, 7858, gene names of H7858; , gene names of CLIP11262. A star designates pseudogenes.

Citation: Buchrieser C, Cossart P. 2007. What Genomics Has Taught Us about Intracellular Pathogens: the Example of , p 361-391. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch14
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Tables

Generic image for table
TABLE 1

General features of published genome sequences

Citation: Buchrieser C, Cossart P. 2007. What Genomics Has Taught Us about Intracellular Pathogens: the Example of , p 361-391. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch14
Generic image for table
TABLE 2

Presence and distribution of internalins, LPXTG, and GW module containing surface proteins in sequenced and

Citation: Buchrieser C, Cossart P. 2007. What Genomics Has Taught Us about Intracellular Pathogens: the Example of , p 361-391. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch14
Generic image for table
TABLE 3

lineage-specific marker genes

Citation: Buchrieser C, Cossart P. 2007. What Genomics Has Taught Us about Intracellular Pathogens: the Example of , p 361-391. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch14

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