ABSTRACTAggregatibacter actinomycetemcomitans is associated with aggressive forms of periodontitis, and with systemic infections such as endocarditis. The cagE gene encodes a ≈39-kDa putative exotoxin expressed by A. actinomycetemcomitans. The prevalence of cagE, and its significance in periodontal disease, has not yet been thoroughly evaluated. In the present study, the role of the cagE gene as a diagnostic marker has been investigated.We have used PCR, and whole genome sequencing data to determine the prevalence of cagE in A. actinomycetemcomitans based on analysis of (i) 249 isolates, collected and cultivated in a Ghanaian longitudinal cohort study, (ii) a serotype b collection of 19 strains, and (iii) the 36 A. actinomycetemcomitans genomes available in the NCBI database.Whereas cagE was absent in the other serotypes, this gene sequence was linked to a virulent and highly leukotoxic group of serotype b strains, including both JP2 and non-JP2 genotypes.We therefore propose that cagE has a potential to be used as a PCR-based gene marker for the identification of a virulent and highly leukotoxic group of serotype b strains, including both JP2 and non-JP2 genotypes. This might be of importance in the risk assessment of the development of periodontal attachment loss in young individuals.