Role of Type VI secretion in polymicrobial oral biofilm communities and in their host interaction

The role of bacterial Type VI secretion systems (T6SS) in human oral ecosystems is unknown. Aggregatibacter aphrophilus is a commensal and the only oral species known to express a T6SS.

Based on our preliminary data, it can kill the periodontal pathogen Aggregatibacter actinomycetemcomitans via its T6SS in vitro.

As the two species exhibit similar niche and colonization requirements in the human host, we hypothesize that A. aphrophilus with its T6SS represents an ecological factor antagonizing A. actinomycetemcomitans.

This novel notion will be tested in the project aims: i) to identify the A. aphrophilus T6SS-dependent effector and immunity proteins by proteomics, construct new mutants and apply them in biofilmcompetition assays with A. actinomycetemcomitans. ii) to define the modulatory role of the A. aphrophilus T6SS during interaction with the host, by co-culturing biofilms with organotypic gingival tissue, followed by proteomics, iii) to determine the structure of the A. aphrophilus T6SS by cryo-EM, and iv) to evaluate the levels of the two species in biofilm samples froma prospective cohort of aggressive periodontitis patients.

The groundbreaking nature of this project rests in the discovery and characterization of T6SS operating in inter-bacterial competition in human oral ecosystems.

Our project is expected to contribute to the development of novel targeted approaches for controlling difficult-to-treat biofilm infections, which will have large socioeconomic impact.