Biofilm infections pose a significant health threat owing to their increased resistance to antibiotics. The oral inflammatory disease periodontitis is caused by a multispecies biofilm. One species associated with periodontitis is the opportunistic pathogen Aggregatibacter actinomycetemcomitans. It produces various virulence factors that contribute to its pathogenicity and survival in the host. The species has been shown to bind and internalize human cytokines, which affect the biofilm composition. Cytokine uptake has the potential to alter host immune responses and bacterial gene expression. Recently it has been suggested that cytokine and DNA uptake could be linked in a naturally competent A. actinomycetemcomitans strain.

This study aimed to provide new knowledge on cytokine binding and uptake, and their proposed connection with DNA uptake in the naturally competent A. actinomycetemcomitans strain D7S. The focus was on two previously studied cytokine-binding outer membrane proteins, the secretin HofQ and the lipoprotein BilRI, along with a type IV pilin homolog, PilA. The functions of PilA have not been previously studied, apart from the discovery that pilA is an essential competence gene. However, type IV pili have been recognized as important virulence factors. Another aim was to study how cytokines alter bacterial gene expression.

This study shows that hofQ and bilRI are involved in the competence of A. actinomycetemcomitans, and that PilA interacts with human cytokines, similar to HofQ and BilRI. The results support the hypothesis that the uptake of cytokines and DNA may occur via the same mechanism. The gene expression studies did not show differences between cytokine-treated and control cultures. However, removal of pilA or hofQ, which are essential for competence, altered gene expression in the competent strain. The changes suggested decreased biofilm formation and virulence.

In addition to cytokine interactions, PilA interacted with human leukocytes. The virulence properties of PilA make it a potential drug target. Meanwhile, BilRI might be involved in survival outside the host, as the activity of the bilRI promoter was increased at lowered temperatures. However, future studies are required to clarify the full potential of PilA and BilRI as virulence factors and the link between cytokine and DNA uptake.