Aggregatibacter actinomycetemcomitans

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Classification

Kingdom: Bacteria; Phylum: Proteobacteria; Class: Gammaproteobacteria; Order: Pasteurellales; Family: Pasteurellaceae; Genus: Aggregatibacter; Species: Actinomycetemcomitans.

Species

NCBI: HK1651 Taxonomy

Description and Significance

Aggregatibacter actinomycetmcomitans is composed of fimbriae, vesicles, and extracellular amorphous materials. These vesicles (blebs) are lipopolysaccharide structures which contain endotoxin. Endotoxin acts as bone resorption and contains actinobacillin, a gram-negative bacterium. Vescicles also serve adhesive properties, allowing the delivery of toxic materials. Fimbriae are small filamentous hair-like appendages that bundle together. They form two types of colonies: fimbriated strains which are star-positive (with a star shape interior) and non-fimbriated strains which are start-negative.

Periodontitis is a serious gum infection, damaging the soft tissue around teeth. Without treatment, periodontitis can lead to tooth loss as well as gum recession. A. actinomycetemcomitans causes rapid progression of localized aggressive periodontitis (LAP). LAP specifically affects incisors and molars, leading to the breakdown of supporting tooth structures if left untreated. For this learson, A. actinomycetemcomitans is considered a systemic pathogen.

Genome Structure

Aggregatibacter actinomycetemcomitans, a bacterium of clinical significance, exhibits a relatively small genome size compared to other bacteria, ranging from 2.0 to 2.7 Mb. Its genome structure is characterized by a single circular chromosome containing 2,206 genes. Among these genes are 2,129 coding sequences, which contribute to various cellular functions, along with 19 rRNAs and 54 tRNAs responsible for protein synthesis. Additionally, the genome harbors 4 noncoding RNAs, which may play regulatory roles within the bacterium. Whole genome sequencing (WGS) studies have revealed that A. actinomycetemcomitans can be divided into three phylogenetic lineages (I, II, and III) based on differences in genomic content and competence for transformation. Furthermore, serotyping, traditionally used for classification, has been shown to be insufficient for accurately characterizing the species, as certain serotypes are not confined to specific lineages.

In addition to its genomic diversity, A. actinomycetemcomitans exhibits variation in competence for transformation, with specific lineages showing varying degrees of natural competence. This competence for transformation is linked to horizontal gene transfer and may impact the genome size of strains within the species. Moreover, WGS studies have challenged traditional taxonomic classifications of A. actinomycetemcomitans based solely on serotyping. Certain strains, such as those in the clade e' outgroup, have been found to fall outside the species boundary based on genomic relatedness. Therefore, while serotyping and WGS provide valuable insights into the genetic diversity and phylogenetic relationships of A. actinomycetemcomitans, the latter offers a more comprehensive understanding of its genome structure, lineage diversity, and taxonomic implications.

Cell Structure, Metabolism and Life Cycle

Aggregatibacter actinomycetemcomitans, a clinically significant bacterium associated with periodontal disease, exhibits distinctive cell structure and metabolism. As a fastidious, facultatively anaerobic, Gram-negative rod, A. actinomycetemcomitans presents unique characteristics. Microscopically, its cells may appear as cocci in broth and clinical samples, indicating potential pleomorphism. Despite its non-motile nature and lack of flagella, this bacterium demonstrates adaptability to environmental conditions, thriving well in 5% CO2 but growing poorly in ambient air. Colonies on chocolate agar are notably small, rough-textured, and tenacious, adhering strongly to agar surfaces. Additionally, A. actinomycetemcomitans is distinguished by its capability to produce important toxins, including leukotoxin, cytolethal distending toxin, and various enzymes, contributing to its pathogenicity in periodontal infections.

Moreover, at the molecular level, A. actinomycetemcomitans is characterized by its outer membrane, which encloses a thin layer of peptidoglycan and an inner cytoplasmic membrane. Its cell shape is rod-shaped, with dimensions typically ranging from 0.4–0.5 µm in width and 1.0–1.5 µm in length. Despite its lack of motility, this bacterium's ability to adhere to surfaces is facilitated by its rough texture, enhancing its colonization and virulence. Metabolically, A. actinomycetemcomitans is capable of producing various toxins crucial for its pathogenicity, contributing to tissue damage and immune evasion in the host. This intricate interplay between cell structure, metabolism, and virulence factors underscores the pathogenic potential of A. actinomycetemcomitans in periodontal diseases and highlights the importance of understanding its biology for effective diagnosis and treatment strategies.

Ecology and Pathogenesis

Aggregatibacter actinomycetemcomitans, a Gram-negative bacterium found in the oral microbiota, plays a significant role in human disease due to its aggregative nature and pathogenic potential. While initially cultured from non-oral infections, its involvement in periodontitis has gained recognition, highlighting its dual capacity to cause both oral and systemic diseases. A. actinomycetemcomitans can be isolated from various oral and non-oral infectious diseases, including infective endocarditis, arthritis, bacteraemia, osteomyelitis, skin infections, urinary tract infections, and abscesses. Its pathogenicity in infective endocarditis is particularly notable, with the bacterium being a member of the HACEK group associated with a small but significant percentage of cases. In the context of periodontitis, A. actinomycetemcomitans contributes to the dysbiotic changes within the periodontal microbiota, leading to inflammatory destruction of connective tissue and bone around teeth. The bacterium's ability to evade host immune responses and interact with other microbial species in the oral cavity underscores its complex role in disease pathogenesis.

Furthermore, A. actinomycetemcomitans is associated with specific virulence factors, notably leukotoxin, which is implicated in localized aggressive periodontitis and can induce apoptosis in epithelial cells, contributing to tissue damage. Additionally, the bacterium produces cytolethal distending toxin (CDT), which disrupts the cell cycle in host cells, leading to DNA damage. Clinical symptoms associated with A. actinomycetemcomitans infections include gingival inflammation, periodontal pocket formation, bone loss, and tooth mobility. The complexity of interactions between A. actinomycetemcomitans, other microbial species, and the host immune system underscores the multifaceted nature of its ecology and pathogenesis, highlighting the need for comprehensive approaches to understanding and managing diseases associated with this bacterium.

Reference

Kelk, P., Abd, H., Claesson, R., Sandström, G., Sjöstedt, A., & Johansson, A. (2011). Cellular and molecular response of human macrophages exposed to Aggregatibacter actinomycetemcomitans leukotoxin. Cell Death & Disease, 2(3), e126–e126.

May, A. C., Ehrlich, R. L., Balashov, S., Ehrlich, G. D., Shanmugam, M., Fine, D. H., ... & Cugini, C. (2016). Complete genome sequence of Aggregatibacter actinomycetemcomitans strain IDH781. Genome Announcements, 4(6), 10-1128.

Nedergaard, S., Kobel, C. M., Nielsen, M. B., Møller, R. T., Jensen, A. B., & Nørskov-Lauritsen, N. (2019). 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. Pathogens, 8(4), 256. ‌

Nørskov-Lauritsen, N., Claesson, R., Jensen, A. B., Åberg, C. H., & Haubek, D. (2019). Aggregatibacter Actinomycetemcomitans: Clinical Significance of a Pathobiont Subjected to Ample Changes in Classification and Nomenclature. Pathogens, 8(4). 

Belibasakis, G. N., Maula, T., Bao, K., Lindholm, M., Bostanci, N., Oscarsson, J., Ihalin, R., & Johansson, A. (2019). Virulence and Pathogenicity Properties of Aggregatibacter actinomycetemcomitans. Pathogens (Basel, Switzerland), 8(4), 222. https://doi.org/10.3390/pathogens8040222