Aggregatibacter actinomycetemcomitans - dissecting the roles of fimbriae and secreted proteins in virulence
The most prevalent disease on planet earth, periodontitis, is an inflammatory disease that destroys soft tissues and bone surrounding our teeth, ultimately leading to tooth loss. Periodontitis is associated with changes in the oral microbial community. In healthy individuals, there is a harmonious coexistence of microorganisms and periodontal tissues. However, this balance can be broken by lifestyle factors, including poor oral hygiene, unhealthy diets and smoking, or antimicrobial therapy. The resulting changes favor oral pathogens, such as Aggregatibacter actinomycetemcomitans, which will exacerbate periodontal disease. The studies described in this thesis provide deeper insights into the contributions of extracellular proteins of different A. actinomycetemcomitans isolates to their growth behavior and virulence. Interestingly, clinical isolates form large aggregates and biofilms on solid surfaces. This feature is rapidly lost upon culturing in the laboratory, which leads to reduced bacterial virulence. Furthermore, the results show that the bacterial aggregation is due to fimbriae on the bacterial surface, which promote bacterial adherence to host cells and allow the delivery of toxins directly to these host cells. The analyses also show that small particles released by the bacteria can neutralize human immune cells, allowing the bacteria to escape from destruction. Altogether, the observations presented in this thesis imply that the bacterial fimbriae are prime targets for preventive and therapeutic interventions against A. actinomycetemcomitans. Such interventions could be achieved with small molecule drugs that break the interaction with host cells, or with immunization approaches, which would both complement present-day treatments based on periodontal care and surgical interventions.