Antagonistic interaction between two key endodontic pathogens Enterococcus faecalis and Fusobacterium nucleatum

ABSTRACT

Background

Endodontic infections are known to be caused by pathogenic bacteria. Numerous previous studies found that both Fusobacterium nucleatum and Enterococcus faecalis are associated with endodontic infections, with Fusobacterium nucleatum more abundant in primary infection while Enterococcus faecalis more abundant in secondary infection. Little is known about the potential interactions between different endodontic pathogens.

Objective

This study aims to investigate the potential interaction between F. nucleatum and E. faecalis via phenotypical and genetic approaches.

Methods

Physical and physiological interactions of F. nucleatum and E. faecalis under both planktonic and biofilm conditions were measured with co-aggregation and competition assays. The mechanisms behind these interactions were revealed with genetic screening and biochemical measurements.

Results

E. faecalis was found to physically bind to F. nucleatum under both in vitro planktonic and biofilm conditions, and this interaction requires F. nucleatum fap2, a galactose-inhibitable adhesin-encoding gene. Under our experimental conditions, E. faecalis exhibits a strong killing ability against F. nucleatum by generating an acidic micro-environment and producing hydrogen peroxide (H₂O₂). Finally, the binding and killing capacities of E. faecalis were found to be necessary to invade and dominate a pre-established in vitro F. nucleatum biofilm.

Conclusions

This study reveals multifaceted mechanisms underlying the physical binding and antagonistic interaction between F. nucleatum and E. faecalis, which could play a potential role in the shift of microbial composition in primary and secondary endodontic infections.

KEYWORDS:

• Interspecies interaction
• coaggregation
• Enterococcus faecalis
• Fusobacterium nucleatum
• fap2
• H₂O₂

Acknowledgments

We thank Jett Liu for help with the language and helpful discussions. We thank Jeffrey McLean, Anne Tanner, Yansong Ma, Jie Nie, Jing Tian, Daniel Ferrer, and Deepak Chouhan for their helpful discussion of this research project.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author Contributions

D. Xiang, contributed to design the experiments, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript; P. Dong, L. Cen, contributed to data interpretation, and critically revised the manuscript; B. Bor and R. Lux, contributed to conception, data interpretation, drafted and critically revised the manuscript; W. Shi, Q. Yu, X. He, and T. Wu, contributed to conception, design, data analysis, interpretation, drafted and critically revised the manuscript. All authors gave final approval and agreed to be accountable for all aspects of the work.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

Research in this publication was supported by the Forsyth institute internal fund and National Natural Science Foundation of China (No. 81870751). Doudou Xiang was partially supported by China Scholarship Council.