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.

Comparative Analysis of Cytokine Expression in Oral Keratinocytes and THP-1 Macrophages in Response to the Most Prevalent Serotypes of Aggregatibacter actinomycetemcomitans

“…In the case of IL-18, a chemokine whose main activity is polynuclear neutrophil attractant with an important role in periodontitis development and described as critical in driving the pathologic breakdown of barrier integrity in different cells models, our results are consistent with those obtained in other studies such as Ando-Suguimoto et al, where the transcription of IL -1β and IL-18 was upregulated in macrophages and oral epithelial cells after 1 h interaction with A. actinomycetemcomitans, and similar to our results, this positive regulation persisted only in macrophages, in our case for 24 h post infection [52].…”

Editorial Comments to the Special Issue: “Aggregatibacter actinomycetemcomitans—Gram-Negative Bacterial Pathogen”

“…In the light of three different reviews, various aspects of the pathobiont Aggregatibacter actinomycetemcomitans have been addressed. The role of this gram-negative facultatively anaerobic bacterium is described by Fine and co-workers [ 1 ]. They proposed that the host response can confine local damage by restricting bacteremic translocation of members of the oral microbiota to distant organs, thus constraining the morbidity and mortality of the host.…”

“…The host response induced by A. actinomycetemcomitans is a challenge for the host and mimic several mechanisms that are associated with processes of degenerative diseases, such as periodontitis [ 1 , 2 ]. In aggressive forms of periodontitis, the dysbiotic microbiota in the subgingival crevice is abundant in A. actinomycetemcomitans.…”

“…Differences in host cell responses between gingival epithelial cells and macrophages led the authors to suggest that survival of A. actinomycetemcomitans in periodontal tissues may be favored by its ability to differentially activate host cells. The most well-studied virulence factor expressed by this bacterium is LtxA, which specifically interacts with human leukocytes [ 1 , 2 ]. Several important discoveries on this toxin have been made by Edward (“Ned”) Lally, who sadly passed away last year, and is a topic of an In Memoriam in this issue [ 9 ].…”

Characterization of Aggregatibacter actinomycetemcomitans Serotype b Strains with Five Different, Including Two Novel, Leukotoxin Promoter Structures

“…The toxin-producing bacterium Aggregatibacter actinomycetemcomitans is associated with periodontitis in young people [ 1 , 2 , 3 , 4 ]. This disease is characterized by a rapid degradation of the tooth-supporting tissues [ 5 ].…”