Tannerella forsythia’s impact on commensal oral biofilm

1) Project file. Modulation of dental plaque interactions with host cells by the periodontal pathogen Tannerella forsythia 2) Content of research project. The oral cavity, similarly to other human organs, is colonized by various microorganisms. Bacterial colonization is controlled by the host immune system and most oral bacteria are beneficial for humans. However, overgrow of some microorganisms might lead to the development of periodontitis, one of the most frequent infectious diseases of adults world-wide, which results in tooth loss, if untreated. In most cases, periodontitis is associated with increased numbers of the "red complex" bacteria - Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia - in the oral biofilm (dental plaque). These bacteria possess specific virulence factors, which facilitate invasion into the human body and cause tissue destruction. Studies in the last years provided evidence that the periodontal pathogen P. gingivalis is able to manipulate distinct components of the host immune system and, consequently, changes the interaction between the oral microbial community as a whole and the immune system. This ability of P. gingivalis is now considered as a key for the progression of periodontitis. 3) Hypothesis. It is currently unclear if other members of the red complex group possess a comparable ability to manipulate the host immune system. Based on own recent data we hypothesize that the periodontal pathogen T. forsythia is an emerging candidate for research into that direction. Thus, this project is designed to investigate T. forsythia for its host-manipulative ability. 4) Methods. To test our hypothesis, we have chosen a combined cell biology / microbiology approach. We will use a biofilm model consisting of five commensal oral microorganisms into which T. forsythia will be incorporated. To delineate effects caused by this pathogen, we will compare the reactions of different human cells involved in the immune response to the biofilm, once with and once without T. forsythia. We will set-up different biofilm-cell co-culture models and we will specifically investigate the biofilm-induced response in epithelial cells, neutrophils, macrophages, and gingival cells, which form the body`s first line of defense against bacterial infection. We will measure several functional parameters involved in the host response against infection and in the control of microbial growth. 5) Explanation indicating what is new/special about the project. The data obtained in this interdisciplinary project will unravel if and how T. forsythia is involved in manipulating the host immune response and disturbing the balance between the immune system and the oral microbial community. The results of this project might pinpoint novel therapeutic and prophylaxis approaches against periodontitis. Above that, learning about new facets of microbial-host interactions will contribute to increasing our general understanding of how bacteria thrive in our body.

Our mouth, like other parts of the body, is home to many different microorganisms. The immune system normally keeps these bacteria in check, and most of them are actually beneficial for our health. Sometimes, however, this delicate balance breaks down, leading to periodontitis-one of the most common infectious diseases among adults in Western countries, causing inflammation and progressive damage to the gums and tooth-supporting tissue. Periodontitis is typically linked to a trio of bacteria known as the "red complex": Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. Earlier research has shown that P. gingivalis can actively interfere with the human immune system to its own advantage, helping it evade defenses and persist in the mouth. In this project, we asked whether T. forsythia, a cohabitant of P. gingivalis, possesses a similar ability-and, importantly, whether this capacity depends on interactions with other bacteria living alongside it. To answer this question, we used two complementary experimental strategies. First, we built an artificial "mini biofilm" containing five harmless bacteria naturally found in the mouth and then introduced T. forsythia into this community. We compared how various human cells reacted to the biofilm with and without this bacterium present. Second, we infected several cell types that form the body's first line of defense against oral bacteria-including gum tissue cells, immune cells called neutrophils and macrophages, and cells from the tooth-supporting ligament-with T. forsythia either alone or together with other bacteria associated with periodontitis, such as P. gingivalis and Fusobacterium nucleatum. We found that T. forsythia triggers a distinct immune response in human cells, clearly different from the response caused by other periodontitis-associated bacteria. Strikingly, when T. forsythia was combined with P. gingivalis, the resulting immune response was considerably stronger than that triggered by either bacterium alone, suggesting that the two pathogens cooperate to intensify inflammation. We further discovered that T. forsythia can flexibly adjust its own metabolism and the production of harmful substances depending on its surroundings, becoming noticeably more aggressive whenever other bacteria are present nearby. Taken together, these findings reveal that T. forsythia is not merely a passive bystander in the mouth, but rather an active player that can team up with other bacteria to manipulate the immune system and worsen gum disease. Gaining a deeper understanding of these bacterial partnerships and how they unfold opens up promising new avenues for developing improved treatments and preventive strategies against periodontitis-a widespread disease that not only affects oral health but has also been linked to several conditions elsewhere in the body, including the heart and joints.