Diminished Treatment Response of Periodontally Diseased Patients Infected with the JP2 Clone ofAggregatibacter(Actinobacillus)actinomycetemcomitans

Abstract

This longitudinal study evaluated the response to periodontal treatment by subjects infected with either JP2 (n ‫؍‬ 25) or non-JP2 (n ‫؍‬ 25) Aggregatibacter (Actinobacillus) actinomycetemcomitans. Participants were treated during the first 4 months by receiving (i) scaling and root planing, (ii) systemic antibiotic therapy, and (iii) periodontal surgery. Probing depth (PD), clinical attachment level (CAL), and gingival and plaque indices (GI and PI, respectively) were monitored at baseline and at 12 months, along with DNA-PCR-based subgingival detection of JP2 or non-JP2 A. actinomycetemcomitans. At baseline, PD, CAL, and GI scores were statistically higher in the JP2 strain-positive group than the non-JP2-strain-positive group. At 12 months, PD, CAL, and GI scores had decreased significantly for both groups, but the reduction rates of PD and CAL were higher in the non-JP2-strain-positive group. Among JP2-strain-positive patients in the baseline, patients who remained JP2 strain positive at 12 months showed significantly higher GIs than did the patients who had lost the detectable JP2 clone. Patients who remained JP2 strain positive at 12 months appeared to be more resistant to mechanical-chemical therapy than did those who were still non-JP2 strain positive, while the elimination of JP2 A. actinomycetemcomitans remarkably diminished gingival inflammation. Early identification and elimination of the JP2 clone of A. actinomycetemcomitans will enable practitioners to effectively predict the outcome of treatments applied to periodontal patients.Compared to gingivitis, or disease-free periodontium, an increased incidence of Aggregatibacter (Actinobacillus) actinomycetemcomitans has been reported in the lesions of localized aggressive periodontitis (LAP) or severe chronic periodontitis (9,13,16,41,44,45). It is also true that while polymicrobial infection is implicated in the pathogenesis of chronic adult periodontitis, oral colonization by A. actinomycetemcomitans is more directly associated with the pathogenesis of LAP. Such pathogenic outcomes related to A. actinomycetemcomitans infection seem to be partially derived from leukotoxin (LTX) produced by A. actinomycetemcomitans. LTX is a potent virulence factor, which is encoded in an operon consisting of four genes (5) and typically causes cytotoxicity in neutrophils (26) and macrophages (37). Furthermore, in vitro experiments revealed that a specific 530-bp sequence in the LTX promoter region, rather than the LTX operon, impacts the transcription regulation of LTX (5), whereas there are several factors that regulate the expression of LTX from A. actinomycetemcomitans (25). It is also true that there may be highly leukotoxic A. actinomycetemcomitans strains other than just the type with the 530-bp deletion (24). Nonetheless, the deletion of this 530-bp promoter region, which is found in some pathogenic strains of A. actinomycetemcomitans, also called JP2 strains, has critical ramifications. For example, faster expression of the LTX gene with the deletion has been o...

The highly leukotoxic JP2 clone ofAggregatibacter actinomycetemcomitansin localized and generalized forms of aggressive periodontitis

“…Alternatively, some of the adolescents may have developed mild disease due to transient infection with the JP2 clone, as it has been found that over a 2-year period approximately half of this age group was temporarily colonized [36], whereas those persistently infected are supposed to develop more severe disease over time, as presumed for the slightly older patient sample included in the present study. In support of this, elimination of the JP2 clone has been shown to correlate with diminishing disease activity [37]. An association between the presence of the JP2 clone of A. actinomycetemcomitans and severity of disease among young adults with AgP is in agreement with results from a previous study on a Brazilian population, where the JP2 clone is also endemically present [26].…”

Antibiotic susceptibility of Aggregatibacter actinomycetemcomitans JP2 in a biofilm

“…The JP2 clone is attributed to descendants of North African populations, but is also prevalent in LAgP patients from other geographical locations (32, 33). It has been shown that A. actinomycetemcomitans JP2 is associated with initiation of periodontal tissue attachment loss (34), and eradication of JP2 provides better outcomes of periodontal treatment (35–37). …”

Effects of low-dose doxycycline on cytokine secretion in human monocytes stimulated with Aggregatibacter actinomycetemcomitans

“…Improving our knowledge of host cytokine regulation in response to bacterial challenge is fundamental to understanding the clinical course of the disease and developing novel treatment strategies for periodontitis (38,39). The clinical impact of LDD in modulating MMP activity is well-described, but its impact on the production of cytokines by monocytes is incomplete.…”