Evolution of the Serotypes of aggregatibacter
Actinomycetemcomitans In Relation to Aggressive
Periodontitis and Geographic Origin of
Individuals – A Review of the Literature
Chi-Cheng Tsai1* and Ying-Chu Lin2
1 School of Dentistry, Chung Shan Medical University, Taiwan
2 College of Dental Medicine, Kaohsiung Medical University, Taiwan
*Corresponding author: Chi Cheng Tsai,
Chung Shan Medical University, Taiwan
Submission:
January 08, 2019;Published: March 13, 2019
Background: Researchers have investigated the relationship among serotype distribution, ethnical status
and geographic populations, and periodontal conditions. Studies that have examined the prevalence and
the distribution of A. actinomycetemcomitans (A.a.) serotypes and the relation between the different
serotypes of the bacterium and periodontal status were reviewed.
Material and methods: A systemic literature search for publications in the database PubMed between
1983 and January 2018 regarding the distribution of A.a. serotypes in subgingival samples of periodontitis
patients and periodontally healthy subjects by various techniques (including culture, immunodiffusion,
immunofluorence, polymerase chain reaction was carried out.
Results: From the cited studies, A.a. bacteria were isolated from various periodontal conditions, including
aggressive periodontitis. Clinical isolates from diverse geographic populations with different periodontal
conditions were summarized. Serotypes a, b and c were largely found, and serotype c was the most
prevalent. The distribution of the most recently identified serotype g remains unknown.
Conclusion: The current literature reviews suggest that serotype a, b, and c are universally dominant,
serotypes d, c and f are rare; the distribution of the most recently identified serotype g still needs more
studies to provide its distribution and its effect on periodontitis. It is widely accepted that distribution
patterns of A.a. vary among subjects of different ethnicity and geographic regions. The importance of
the identification of A.a. and their antibiotic susceptibility tests prior to the treatments of periodontitis
especially for aggressive periodontitis and peri-implantitis concomitantly to periodontal therapy are
strongly advised.
Aggressive periodontitis is a severe and rapidly progressing form of periodontitis [1,2] that
affecting supporting tissues of the teeth induced by microbial deposits [3]. Aggregatibacter
actinimycetemcomitans is an important pathogen related to aggressively progressive
periodontal breakdown in adolescents and adults [4,5]. A. actinomycetemcomitans (A.a.) can
be grouped into seven serotypes (a-g) [6,7]. Several studies have examined the relationship of
A.a. serotype, ethnical status and geographic populations, periodontal disease status [8,9,10].
Individuals are usually colonized by a single serotype that can exist for life [8,11,12]. The
frequency distribution of A.a. serotypes differs among various populations [13]. The available
literature suggests that serotypes a, b. and c occur much more often among oral isolates than
d, e, f and g [14,15,16]. The serotype distributions have been shown to be different among
various geographic populations including African, Asian, Europeans, and North and South
American [15,16,17,18,19]. The purpose of the present study was to review the studies that
have investigated the prevalence and the distribution of A.a. serotypes in subgingival samples
of periodontitis (especially the aggressive periodontitis) patients
and to examine the possible evolution of the serotypes.
The electronic database PubMed was searched systemically
for studies published between 1983 and January 2018. The
search terms included “serotypes” and “Aggregatibacter
Actinomycetemcomitans” or “Acticbacillus actinomycetemcomitans”
and “periodontitis”.
Study selection
Studies involving the distribution of A.a. serotypes in subgingival
samples of periodontitis patients and periodontally healthy
subjects by employing culture, indirect immunofluorescence and/
or immunodiffusion assays, and polymerase chain reaction (PCR)
were eligible for inclusion in this review. Data were extracted from
each study:
(a) the first author and year of publication;
(b) the country where the study was investigated;
(c) searched serotypes and
(d) possible association between periodontal conditions and
serotypes.
Forty-two articles were identified. The full text/abstract of
each of the 42 papers was reviewed. The study selections are
presented in Table 1. The publication dates ranged from 1983 to
2018. Clinical isolates from diverse geographic populations with
different periodontal conditions were evaluated. The samples were
obtained of the subjects from Brazil, Germany, Greece, Indonesia,
Japan, Korea, Taiwan, Thailand and United States (US) etc. Table 1
shows the prevalence and distribution of A.a. serotypes a, b and c
were largely found, and serotype c was the most prevalent. These
serotypes were isolated from various periodontal conditions,
including aggressive periodontitis. Serotypes d, e, f and g were
either not detected or were relatively infrequent. Some A.a. isolates
were non-typed.
Table 1:Prevalence and distribution of A. actinomycetemcomitans (A.a.) serotypes and association with periodontal
status. LAgP: Localized Aggressive Periodontitis. CP: Chronic Periodontitis, JP: Juvenile Periodontitis.
It is convinced that the differences in serotypes distribution
related to geography and/or ethnic group. The current presented
data indicate that the geographic distribution of serotypes is not
uniform [4,40,43,49]. The distribution pattern of A.a. serotypes
varies greatly depending on the periodontal status of the allocated
population and the country where the study takes place [30,32,35
,40,43,45,47,49,52,53,58]. Some studies suggest that different A.a.
serotypes are associated with periodontal health, periodontitis
[6,10,15,18,31,34,39,49,52,57]. It is suggested that patients are
usually infected by one serotype and colonization is stable over
time [8,36,37], however occasional individuals are infected with
two or three serotypes [34,37,39,40,44,47,52,545,57,59]. Most
investigators found relatively low frequencies of multiple–serotype
infection, except a study in Japan that shows 2 or 3 serotypes of
A.a. with a frequency of 33% of the sites tested [31]. In general, the
serotypes a-c occurred much more frequently among oral isolates
than serotypes d-g. In African-Americans, a, b, and c serotypes
seem to be distributed in equal frequencies, whereas in Hispanic
subjects, a strong association with serotype c was reported [34].
In Greece [43], serotype a, b, and c were largely found to be equally
distributed. In Brazilian population, the serotypes are in majority of
a, b and c (up to 98%), with the serotype c most prevalent. Serotypes
d, e, and f were either rare or not-detected [16,40,46]. In 2010 Chen
et al. [41] reported that the serotype c is the dominant serotype
followed by serotypes of a, and b, the d, e, and f were either not
detected or relatively rare in the United States [41]. This is greatly
different from the previous reported.
Almost all the studies showed that the Asian populations were
commonly infected with A.a. serotype c, but occasionally colonized
with serotype b [15,21,22,25-27,30,31,35-37,48,50-53,55,57,58].
In Taiwan, two studies demonstrated that the c serotype was the
predominant [21,58], other studies found that serotype b was
more than c or other serotypes [15,32]. In contrast, serotype b was
commonly observed in Caucasian populations [37] and in German
patients [37]. The serotype distribution pattern of A.a. within a local
population may change over time, as seen in Indonesian periodontitis
patients between 1994 to 2002 [36]. Serotypes d-f were rarely
detected in most populations worldwide [40,42,45], however, a high
prevalence of serotype e (19-47%) was noted in Indonesian [36]
and Japanese [31]. JP2 (serotype b) strain with super-leukotoxicity
was discovered in 1979 by the authors of Tsai et al. [61]. In Japan,
serotype c was predominantly identified in the gingival tissues of
LAgP patients [31], and the distribution of serotypes was influenced
by the presence of P. gingivalis (P.g.). The longitudinal follow-up
study in Indonesia demonstrated that the mean increase in probing
pocket depth between 1994 and 2002 was significantly greater
in subjects’ culture positive in 2002 in comparison to subjects
without detectable A. actinomycetemcomitans (A.a.) in 2002 [36].
The shifts of the predominant serotype b to a more prevalence as
evidenced by the studies in Indonesia and in the United States [41]
might be explained to some extent, associated with the periodontal
treatment including the use of antibiotics, and the high titer of
antibody levels to predominant infected serotypes of A.a. The high
levels of anti-A.a. antibody together with viable polymorphonuclear
neutrophils (PMNs) and complement could more efficiently kill
the infecting A.a. [62]. Thirdly, some previous studies classified
serotype f as serotype b due to the serological cross-reactivity with
anti-serotype b-specific antiserum [29]. Fourthly, study has shown
that the recombination between strains of the same A.a. serotype
appears to take place in nature, suggesting that non-serotypeable
strains are serotype antigen-deficient variants originating from
strains of the known serotypes [63]. In Brazil, AgP subjects were
not exclusively associated with A.a. serotype b [40,46]. Isolates
from healthy subjects belong to serotype c or a [46]. Serotype c was
the most A.a., and was isolated from various periodontal conditions,
including AgP [45]. In Greek population, A.a. was more prevalent in
untreated periodontitis subjects, but no clear predominance of a
specific A.a. serotype and absence of the JP2 clone were observed
[43]. In Sweden, the findings indicate that periodontitis affecting
the primary dentition does not necessary leads to the presence of
periodontal attachment loss in the permanent dentition [39].
The JP2 clone shows a limited geographical and ethnic host
range, predisposing in subjects with an African lineage, but absent
from non-African population from Northern Europe [14,65].
However, Claesson et al. [44] found that Caucasians can carry the
JP2 clone of A. actinomycetemcomitans. The studies cited in this
review have varied widely in periodontal disease diagnosis and
status, sampling protocols, study design and microbial detection
methods and serotype analysis techniques. The periodontal therapy
aims to the elimination of A.a. from periodontal pockets has been
shown to be correlated with the outcomes of therapy. Akrivopoulou
et al. [59] studied the prevalence of A.a. serotypes and reported
that of the 56 isolates tested, 100% were resistant to penicillin and
metronidazole, 87.5% to clindamycin, 83.9% to amoxicillin and
76.8% to ceftazidime; low rates of resistance to tetracycline (8.9%
resistant) and 2013; 5:20320. http//dx.dol.org/10.3402/jom.
v510.20320. amoxicillin/clavulanic acid (14.3%); no isolates were
resistant to ciprofloxacin.
In the study of the antibiotic resistance in human periimplantitis
microbiota, Ramus et al. [64] reported that all six A.a.
subject strains exhibited in vitro resistance to clindamycin, and
five to doxycycline, whereas none were resistant in vitro to either
amoxicillin, metronidazole or amoxicillin plus metronidazole [65].
However, adjunctive systemic amoxicillin plus metronidazole
medication to scaling and root planing (SRP) significantly improved
the clinical outcomes with respect to mean probing pocket depth,
clinical attachment loss compared to SRP alone [66]. In contrast,
Aggregatibacter actinomycetemcomitans JP2 homotypic biofilms
were more susceptible in vitro to doxycycline than amoxicillin plus
metronidazole [66]. Such results highlight the need for culture
and antibiotic susceptibility tests in patients with aggressive
periodontitis (AgP) and patients with peri-implantitis prior to
systemic use of antibiotics concomitantly to periodontal therapy.
In conclusion, this review indicates that different ethnic groups
are preferentially colonized by different A. actinimycetemcomitans
serotypes and the relationship between different A.a. serotypes and
periodontal conditions remains to be investigated in the future.
Professor, Chief Doctor, Director of Department of Pediatric Surgery, Associate Director of Department of Surgery, Doctoral Supervisor Tongji hospital, Tongji medical college, Huazhong University of Science and Technology
Senior Research Engineer and Professor, Center for Refining and Petrochemicals, Research Institute, King Fahd University of Petroleum and Minerals (KFUPM), Dhahran, Saudi Arabia
Interim Dean, College of Education and Health Sciences, Director of Biomechanics Laboratory, Sport Science Innovation Program, Bridgewater State University