MICROBIOLOGY (M KLEIN, SECTION EDITOR) Challenges in the Eradication of Enterococcus faecalis and its Implications on Health Eyal Rosen 1 & Ilana Kolodkin-Gal 2 & Igor Tsesis 1 # Springer International Publishing AG, part of Springer Nature 2018 Abstract Enterococcus faecalis is frequently found in infected root canals of teeth with persistent apical periodontitis. Purpose To review the challenges involved in the eradication of persistent Enterococcus faecalis infections and their impact on human health. Recent Findings In the root canal system, Enterococcus faecalis resides in biofilm communities that are able to resist a wide range of harsh conditions and treatments and persist for years. Various virulence and resistance factors provide Enterococcus faecalis capabilities in adherence, colonization, and biofilm formation, which is much more resistant to antibacterial agents than planktonic bacteria. These capabilities explain its persistence in root canal infections. To date, the available therapeutic tools to efficiently eradicate Enterococcus faecalis infections remain limited. Recently, in a model mimicking Enterococcus faecalis root canal infection, novel biofilm inhibitors and dispersing agents, such as D-Leucine, presented superior capability over sodium hypochlorite, the frequently used root-canal antibacterial irrigation solution, in the eradication of Enterococcus faecalis. Summary These recent studies present promising treatment regimens for Enterococcus faecalis persistent infections. Keywords Enterococcus faecalis . Biofilm . Root canal . Eradication . Health implications Introduction Despite the commonly held concept of bacteria as unicellular organisms that fight for individual survival, in nature, bacteria usually form complex communities, termed biofilms, that are stimulated by chemical cues. A biofilm is an ecological com- munity, where the inhabitant bacteria are detained together by an extracellular matrix. In a biofilm, bacteria use different mechanisms to align their activity within the community, as well as across species, to achieve complex multicellular activ- ities [1–4]. One main characteristic of biofilms, and part of the definition of what constitutes a biofilm, is the existence of a self-produced extracellular matrix (ECM) that surrounds and protects the cells and makes them adhere to each other or to a surface [5]. The main components of bacterial ECM are the following: (i) extracellular polysaccharides or exopo lysaccharides, (ii) proteins, and (iii) nucleic acids [5]. These extracellular matrices hold the single bacteria together to form a multicellular community [5–8, 9•]. When compared to planktonic (free-living) state, cells in biofilms are more protected from environmental insults, including sterilizing agents, antibiotics, and the immune system. Biofilms enable bacteria to attach more firmly to their hosts and to have better access to nutrients [10–16]. Microbial biofilms represent most of the microbial in- fections in the human body [6, 11–13, 15], and can cause life-threatening infections [17]. Biofilm infections are par- ticularly challenging in medical settings where resistance to antimicrobial agents is a major problem [ 9• , 18]. Biofilms are also the main source of apical periodontitis [ 9 • , 19 ], an inflammatory response induced in the periapical tissues surrounding the tooth root due to micro- bial penetration and colonization within the root canals. These intra-canal bacterial communities produce by- products and toxins that stimulate the periapical inflam- mation and subsequent tissue destruction [9•, 20]. This article is part of the Topical Collection on Microbiology * Eyal Rosen dr.eyalrosen@gmail.com 1 Department of Endodontology, Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel 2 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel Current Oral Health Reports https://doi.org/10.1007/s40496-018-0172-4