VIRULENCE FACTORS OF ENTEROCOCCUS FAECALIS: RELATIONSHIP TO ENDODONTIC DISEASE

VIRULENCE FACTORS OF ENTEROCOCCUS FAECALIS: RELATIONSHIP TO ENDODONTIC DISEASE
2004
G?ven Kayaoglu*
Dag ?rstavik
Critical Reviews in Oral Biology & Medicine

Š 2004 International and American Associations for Dental Research

1 Gazi University, Faculty of Dentistry, Department of Endodontics and Conservative Treatment, 82. Sokak 06510 Emek, Ankara, Turkey; 2 NIOM, Scandinavian Institute of Dental Materials, Haslum, Norway

* corresponding author, guvenk@gazi.edu.tr

Abstract

Enterococcus faecalis is a micro-organism that can survive extreme challenges. Its pathogenicity ranges from life-threatening diseases in compromised individuals to less severe conditions, such as infection of obturated root canals with chronic apical periodontitis. In the latter situation, the infecting organisms are partly shielded from the defense mechanisms of the body. In this article, we review the virulence factors of E. faecalis that may be related to endodontic infection and the periradicular inflammatory response. The most-cited virulence factors are aggregation substance, surface adhesins, sex pheromones, lipoteichoic acid, extracellular superoxide production, the lytic enzymes gelatinase and hyaluronidase, and the toxin cytolysin. Each of them may be associated with various stages of an endodontic infection as well as with periapical inflammation. While some products of the bacterium may be directly linked to damage of the periradicular tissues, a large part of the tissue damage is probably mediated by the host response to the bacterium and its products.
Key words. Enterococcus faecalis, virulence factors, endodontic infection, apical periodontitis

Introduction

Enterococci inhabit the gastrointestinal tract, the oral cavity, and the vagina in humans as normal commensals. They can cause a wide variety of diseases in humans, infecting the urinary tract, bloodstream, endocardium, abdomen, biliary tract, burn wounds, and indwelling foreign devices (Jett et al., 1994). Enterococci now rank among the top three nosocomial bacterial pathogens (Richards et al., 2000; Wisplinghoff et al., 2003), and strains resistant to currently available antibiotics pose real therapeutic difficulties (Hunt, 1998). Up to 90% of enterococcal infections in humans are caused by Enterococcus faecalis. The majority of the remainder is caused by Enterococcus faecium, and infections with the other species are quite rare (Jett et al., 1994). Enterococci have also been implicated in endodontic infections. Although they make up only a small proportion of the initial flora of untreated teeth with necrotic pulps (Sundqvist, 1992), enterococci, particularly E. faecalis, have been frequently found in obturated root canals exhibiting signs of chronic apical periodontitis, isolated in 23Ň70% of the positive cultures (Engstrŕm, 1964; Mŕller, 1966; Molander et al., 1998; Sundqvist et al., 1998; Peciuliene et al., 2000; Hancock et al., 2001) and often occur in monoculture (Sundqvist et al., 1998; Dahlťn et al., 2000; Peciuliene et al., 2000; Hancock et al., 2001). Moreover, E. faecalis was among a group of bacteria cultured from periapical lesions refractory to endodontic treatment (Sunde et al., 2002).

Enterococci can withstand harsh environmental conditions. As originally defined by Sherman (1937), enterococci can grow at 10?C and 45?C, at pH 9.6, in 6.5% NaCl broth, and survive at 60?C for 30 minutes. E. faecalis can adapt to adverse conditions: Following pre-exposure to sublethal stress conditions, E. faecalis becomes less sensitive to normally lethal levels of sodium dodecyl sulfate, bile salts, hyperosmolarity, heat, ethanol, hydrogen peroxide, acidity, and alkalinity; furthermore, Îcross-protectionĚ is pronounced against diverse challenges (Flahaut et al., 1996a,b,c, 1997). Starving E. faecalis cells maintain their viability for extended periods and become resistant to UV irradiation, heat, sodium hypochlorite, hydrogen peroxide, ethanol, and acid (Giard et al., 1996; Hartke et al., 1998). E. faecalis, moreover, can enter the viable but non-cultivable (VBNC) state, a survival mechanism adopted by a group of bacteria when exposed to environmental stress, and resuscitate upon returning to favorable conditions (Lle? et al., 2001). The ability of E. faecalis to tolerate or adapt to harsh environmental conditions may act as an advantage over other species. It may explain its survival in root canal infections, where nutrients are scarce and there are limited means of escape from root canal medicaments.

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