From Global to Nano: A Geographical Perspective of Aggregatibacter actinomycetemcomitans

Abstract

The periodontal disease pathobiont Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) may exert a range of detrimental effects on periodontal diseases in general and, more specifically, with the initiation and progression of Localized Stage III Grade C periodontitis (molar-incisor pattern). In this review of the biogeography of this pathobiont, the full range of geographical scales for A. actinomycetemcomitans, from global origins and transmission to local geographical regions, to more locally exposed probands and families, to the individual host, down to the oral cavity, and finally, to spatial interactions with other commensals and pathobionts within the plaque biofilms at the micron/nanoscale, are reviewed. Using the newest technologies in genetics, imaging, in vitro cultures, and other research disciplines, investigators may be able to gain new insights to the role of this pathobiont in the unique initial destructive patterns of Localized Stage III Grade C periodontitis. These findings may incorporate the unique features of the microbiome that are influenced by variations in the geographic environment within the entire mouth. Additional insights into the geographic distribution of molar-incisor periodontal breakdown for Localized Stage III Grade C periodontitis may derive from the spatial interactions between A. actinomycetemcomitans and other pathobionts such as Porphyromonas gingivalis, Filifactor aclocis, and commensals such as Streptococcus gordonii. In addition, while the association of A. actinomycetemcomitans in systemic diseases is limited at the present time, future studies into possible periodontal disease-systemic disease links may also find A. actinomycetemcomitans and its geographical interactions with other microbiome members to provide important clues as to implications of pathobiological communications.

Keywords: Aggregatibacter actinomycetemcomitans; Localized Stage III Grade C periodontitis; Porphyromonas gingivalis; aggressive periodontitis; biofilms; biogeography.

Figure 3

A proposed geographical model distribution of A. actinomycetemcomitans in the plaque biofilm based on diverse prior imaging studies and in vitro studies [76,81,82,83]. (1) A. actinomycetemcomitans may cluster around streptococcus “corncob” formations at the end of the filamentous corynebacterium species and may also form clusters near other pathobionts such as P. gingivalis. (2) However, gingipain enzymes from P. gingivalis may also exclude A. actinomycetemcomitans from areas of the plaque biofilm and prevent aggregation within the biofilm (original image created by the author for this manuscript with Biorender.com).

Figure 1

A proposed geographical origin and pathway of dissemination of A. actinomycetemcomitans in the African American population through genetic back tracing: 1. Origin from North Africa to West Central Africa and then to 2. North and South America through the slave trade [14,15,16]. 3. Regarding the spread to other parts of the world where A. actinomycetemcomitans may have disseminated and been detected, these geographical routes have yet to be determined but may include discrete geographic zones, such as regions of Sweden [16,17] (original image created by the author for this manuscript with Biorender.com).

Figure 2

Differences in physical geography of the oral cavity that may affect regional variations of the location and distribution of A. actinomycetemcomitans may include tooth location, tooth type, and tooth surface; temperature gradients from the anterior to posterior oral cavity; attachment to different mucosal surfaces; location of the salivary ducts, salivary composition, and differences in salivary flow; effects of the cheek, tongue, and masticatory musculature; regional variations in the quantity of plaque accumulation; and chemical and physical characteristics of the diet (original image created by the author for this manuscript with Biorender.com).

Figure 4

“Fight/Flight interactions between A. actinomycetemcomitans and S. gordonii. (1) At the closest geographical distances between these two microbial species, the beneficial effects of lactate production from S. gordonii on the growth of A actinomycetemcomitans are offset by the higher toxic concentrations of H₂O₂. (2) However, the production of dipersin B by A. actinomycetemcomitans facilitates a separation from S. gordonii and an exposure to a lower and less toxic concentration of H₂O₂, which can be neutralized by catalases from A. actinomycetemcomitans, stimulate resistance to complement from the host response, and maintain some of the nutritional benefits of S. gordonii produced lactate (original image created by the author for this manuscript with Biorender.com).