Whole Genome Sequencing of Aggregatibacter actinomycetemcomitans Cultured from Blood Stream Infections Reveals Three Major Phylogenetic Groups Including a Novel Lineage Expressing Serotype a Membrane O Polysaccharide

Abstract

Twenty-nine strains of Aggregatibacter actinomycetemcomitans cultured from blood stream infections in Denmark were characterised. Serotyping was unremarkable, with almost equal proportions of the three major types plus a single serotype e strain. Whole genome sequencing positioned the serotype e strain outside the species boundary; moreover, one of the serotype a strains was unrelated to other strains of the major serotypes and to deposited sequences in the public databases. We identified five additional strains of this type in our collections. The particularity of the group was corroborated by phylogenetic analysis of concatenated core genes present in all strains of the species, and by uneven distribution of accessory genes only present in a subset of strains. Currently, the most accurate depiction of A. actinomycetemcomitans is a division into three lineages that differ in genomic content and competence for transformation. The clinical relevance of the different lineages is not known, and even strains excluded from the species sensu stricto can cause serious human infections. Serotyping is insufficient for characterisation, and serotypes a and e are not confined to specific lineages.

Aggregatibacter Actinomycetemcomitans: Clinical Significance of a Pathobiont Subjected to Ample Changes in Classification and Nomenclature

“…A recent study compared whole genome sequences of strains from blood stream infections supplemented with oral reference strains [46]. Exclusion of so-called clade e' strains increased the number of core genes present in all strains from 1146 to 1357.…”

“…In contrast to lineage I, many strains of different serotypes from this lineage are competent for natural transformation, and the average size of genomes is approximately 10% larger than in lineage I. Lineage III also expresses St(a) membrane O polysaccharide, and the genome size is comparable to lineage II. However, all six investigated strains were incompetent for transformation due to inactivation of multiple competence genes [46].…”

“…well as the rhesus macaque monkey strain) may possibly be transferred to new species, and A. actinomycetemcomitans may be restricted to strains with exclusive host specificity for humans. A recent study compared whole genome sequences of strains from blood stream infections supplemented with oral reference strains [46]. Exclusion of so-called clade e' strains increased the number of core genes present in all strains from 1146 to 1357.…”

Aggregatibacter, a Low Abundance Pathobiont That Influences Biogeography, Microbial Dysbiosis, and Host Defense Capabilities in Periodontitis: The History of a Bug, and Localization of Disease

“…This review is written as an overall appraisal of a field of research that has been part of a personal journey related to a specific microorganism (Aggregatibacter actinomycetemcomitans) and its relationship to a specific form of periodontal disease (Localized Aggressive Periodontitis, LAgP). The review is not presented as a systematic review of the literature (several reviews on this topic already exist [1][2][3][4][5][6]) but rather as a critical but broad interpretation of the field of research based on studies done by members of our laboratory and others in the field. The review offers novel ways of assessing infectious diseases from the point of view of the microbe, its host, and particularly interactions between the microbe and its host.…”

Aggregatibacter Actinomycetemcomitans: Clinical Significance of a Pathobiont Subjected to Ample Changes in Classification and Nomenclature

“…In contrast to lineage I, many strains of different serotypes from this lineage are competent for natural transformation, and the average size of genomes is circa 10% larger than in lineage I. Lineage III also expresses St(a) membrane O polysaccharide, and the genome size is comparable to lineage II. However, all six investigated strains were incompetent for transformation due to insertions in the comM gene[46].In conclusion, St designations are valuable for initial typing of clinical strains, but insufficient for characterisation. Recognition of a general MLST scheme could be helpful, and whole genome sequences could be used for MLST and in silico serotyping, as well as further characterisation and epidemiologic investigations.…”