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Chapter 8 : The Aggregatibacter actinomycetemcomitans Genome: Diversity of Pathogenic Potential
Category: Genomics and Bioinformatics
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Aggregatibacter actinomycetemcomitans is a small, gram-negative, facultatively anaerobic coccobacillus that belongs in the family Pasteurellaceae. A localized form of the disease, localized aggressive periodontitis, was originally found to be associated with the presence of A. actinomycetemcomitans in periodontal pockets. Genetic analyses show that the JP2 clone constitutes a subpopulation of restriction fragment length polymorphism (RFLP) group II. All isolates of the JP2 clone are serotype b, are identical in multilocus enzyme electrophoresis, and have the same DNA fingerprint using the restriction enzyme MspI, but show variation in ribotype. The RFLP group II strains, including strain JP2, have elevated expression of cytolethal distending toxin (CDT) measured as cytotoxicity for Chinese hamster ovary cells. Genomic islands that carry the leukotoxin gene cluster, the lipooligosaccharide biosynthesis gene cluster, the tight adherence gene cluster, and the CDT gene cluster are common to HK1651, D11S-1, and D7S-1 strains, whereas the other islands are strain specific. Members of the author's group used multilocus sequence analysis to study microevolution of the JP2 clone. Based on the assumptions that the variations were caused by single-site mutations and that each mutation occurred only once, it was possible to deduce an evolutionary model for A. actinomycetemcomitans serotype b, including the origin of the JP2 clone.
Map of the leukotoxin (ltx) operon in A. actinomycetemcomitans. The genes in the ltx operon are labeled A to D where ltxA is the structural gene, the gene product of ltxC is required for activation of the toxin, and ltxB and ltxD encode proteins that assist in secretion of the toxin. The 530-bp deletion in the promoter region in strains of the JP2 clone is indicated by dashed lines, and the insertion sequence found in a Japanese strain is denoted IS.
Phylogenetic tree constructed on the basis of substitutions in the partial genome sequences. The core segments, shared by all strains, of a Mauve alignment of the four A. actinomycetemcomitans were used for tree construction.
DNA asymmetry and DnaA box distribution on the chromosome of A. actinomycetemcomitans strain HK1651. Chromosome coordinates are shown on the x axis beginning with the dnaA gene as in the databases. The gray line and the right y axis show the (G-C) DNA asymmetry. Black vertical lines with diamonds and the left y axis show the DnaA box distribution and a peak indicates presence of a cluster of three close DnaA boxes as described previously ( 52 ). The figure was kindly provided by P. Mackiewicz.
Genetic distance between strains of A. actinomycetemcomitans serotype b, measured as the frequency of substitutions in homologous sequences in the aligned genomes