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

Abstract

Aggregatibacter actinomycetemcomitans, the focus of this review, was initially proposed as a microbe directly related to a phenotypically distinct form of periodontitis called localized juvenile periodontitis. At the time, it seemed as if specific microbes were implicated as the cause of distinct forms of disease. Over the years, much has changed. The sense that specific microbes relate to distinct forms of disease has been challenged, as has the sense that distinct forms of periodontitis exist. This review consists of two components. The first part is presented as a detective story where we attempt to determine what role, if any, Aggregatibacter plays as a participant in disease. The second part describes landscape ecology in the context of how the host environment shapes the framework of local microbial dysbiosis. We then conjecture as to how the local host response may limit the damage caused by pathobionts. We propose that the host may overcome the constant barrage of a dysbiotic microbiota by confining it to a local tooth site. We conclude speculating that the host response can confine local damage by restricting bacteremic translocation of members of the oral microbiota to distant organs thus constraining morbidity and mortality of the host.

Keywords: Aggregatibacter actinomycetemcomitans; bacteremia; damage/response framework; horseshoe crab; landscape ecology; leukotoxin; localized aggressive periodontitis: animal studies: human studies.

Figure 1

Radiograph of subject with Localized Aggressive Periodontitis: Panoramic radiograph showing extreme bone loss in first molar on left side in a 19-year-old patient.

Figure 2

A. actinomycetemcomitans abiotic surfaces. A. actinomycetemcomitans was inoculated into a flask and allowed to grow on the side of the flask for three days. The flask on the left is an un-inoculated control. The flask on the right shows binding of A. actinomycetemcomitans to the side of the flask and no microbes can be found in the media. The insert in the center is the colonial morphology of A. actinomycetemcomitans showing star on top and rough colonial outer surface.

Figure 3

Phylogenetic analysis of the tad operon in a various microbial species. Illustration of the widespread colonization island (wci). WCI is a 14-gene operon. The top three microorganisms have the complete tad operon. The others have portions of it. WCI is present in many pathobionts and all archae sequenced to date.

Figure 4

Binding of human A. actinomycetemcomitans to buccal epithelial cells (BECs). A. actinomycetemcomitans binds to BECs from Old World primates but not from New World primates. Mutation of the aae gene significantly reduces binding in these primates.

Figure 5

Kinetics of binding of A. actinomycetemcomitans to buccal epithelial cells (BECs).

Figure 6

Microbial plaque development over time. Plaque starts above the gingival margin and progresses to the subgingival environment where it eventually encounters polymorphonuclear leukocytes (PMNs) along with complement in an attempt by the host to limit the accumulating biofilm from invading the underlying tissue.

Figure 7

The fibrin cascade simplified. Prothrombin activator enzymatically cleaves prothrombin, which then activates thrombin that is now available to cleave fibrinogen to fibrin. Fibrin is acted on by plasmin to form a clot in a manner similar to that seen in the horseshoe crab.