Chapter 7 : Pathogenomics: Genomes and Beyond

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Members of the genus are defined as fastidious, microaerophilic, oxidase positive, nonfermentative, gram-negative bacteria. All predicted proteins from the five genomes were compared with data from other published microbial genomes by BLASTP. The chromosomes of all five strains in this comparative study were examined for the presence or absence of clustered regularly interspaced short palindromic repeats (CRISPR) elements in intergenic regions. In this study, a strain is considered CRISPR positive when it contains two or more direct repeats of a 21-bp or larger DNA segment separated by unique spacer sequences of a similar size. The species strains analyzed in this study have the Sec-dependent and Sec-independent protein export pathways for the secretion of proteins across the inner or periplasmic membrane. Of the 580 open reading frames (ORFs) conserved between the and species included in this study, 27 ORFs involved in flagellar biosynthesis and function were conserved between and . A research group applied in vitro -based transposition system to identify genes involved in motility in 81-176. They followed up this work to show that flagellar genes were regulated by σ, but not σ. Although some proteomic studies have been conducted for , these were limited to differential analysis of specific mutations, planktonic versus biofilm growth, and on NCTC 11168 stocks with different amounts of passaging.

Citation: Fouts D, Mongodin E, Nelson K. 2007. Pathogenomics: Genomes and Beyond, p 160-195. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch7
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Schematic illustration comparing the steps of invasion and pathogenesis of the gastrointestinal pathogens and . (A) Schematic representation of the human gastrointestinal tract and sites of colonization of , largely confined to the antrum (part of the stomach that lacks acid-secreting parietal cells) and , which targets the ileal-colonic epithelial cells. (B) Invasion mechanisms of . probably adheres first to microvilli-containing regions of gastric epithelial cells (step 1). After adherence, microvilli are denuded and tight junctions disrupted under the action of urease; the VacA toxin is probably also involved in this process (step 2). Cuplike projections and pedestals form, accompanied by actin polymerization and cytoskeletal rearrangements (steps 2 and 3). Bacterial genes involved in the steps immediately after adherence are still poorly understood, and it is not clear at what stage rare bacteria become internalized (step 4a). Genes from the (cytotoxin-associated gene) pathogenicity island are implicated in the postadherence mechanism of infection (step 4b) and are responsible for the induction of an intense inflammatory reaction. (C) pathogenesis. adheres to the apical cell surface of the perijunctional region of the intestinal epithelium (step 1). Among the multiple bacterial adhesions that are thought to be involved in adherence to intestinal epithelial cells are the 37k-Da adhesin CadF (which is believed to target the host fibronectin receptors), PEB1, JlpA, and a 43-kDa major outer membrane protein. Attached bacteria then secrete invasion effectors into the host cells (step 2), among which the 73-kDa secreted protein CiaB, resulting in the phosphorylation of host proteins and the release of Ca from intracellular stores. Host signaling cascades trigger a localized disruption of cortical actin filaments and an extension of microtubules to form a membrane extension (step 3), resulting in the endocytosis of the cells (step 4). The vacuole-engulfed bacterium (step 5) then moves via dynein along the microtubules to the baso-lateral surface for exocytosis (step 6). Infected cells release interleukin-8 basolaterally, which enlists lymphocytes from the lamina propria. The two schematic illustrations in (B) and (C) were modified from ( ) and ( ).

Citation: Fouts D, Mongodin E, Nelson K. 2007. Pathogenomics: Genomes and Beyond, p 160-195. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch7
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Image of FIGURE 2

Phylogenetic analysis. Consensus maximum-likelihood trees are depicted using multiple alignments of 16S rRNA (A) or 12 concatenated protein data sets (B). The numbers along the branches denote percent occurrence of nodes among 100 bootstrap replicates. The scale bar represents the number of nucleotide (A) or amino acid (B) substitutions.

Citation: Fouts D, Mongodin E, Nelson K. 2007. Pathogenomics: Genomes and Beyond, p 160-195. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch7
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Image of FIGURE 3

Main pathways for metabolism derived from an analysis of five genomes. The tricarboxylic (TCA) cycle has major variations based on comparative analysis across the strains (see text). Differences in substrate respiration are based on an analysis of Biolog data, and species-specific pathways are presented in the text.

Citation: Fouts D, Mongodin E, Nelson K. 2007. Pathogenomics: Genomes and Beyond, p 160-195. In Pallen M, Nelson K, Preston G (ed), Bacterial Pathogenomics. ASM Press, Washington, DC. doi: 10.1128/9781555815530.ch7
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