Two-component signal transduction in Enterococcus faecalis.

Enterococci are gram-positive constituents of the normal human microflora, typically colonizing the intestinal tract and skin (34, 47). However, these organisms are capable of causing disease as opportunistic pathogens, mainly in immunocompromised patients (35, 58). The problem of enterococcal infection has been aggravated by the emergence in the past decade of multiple antibiotic resistance, which has converted some enterococci from being difficult to treat medically to being completely refractory to all antimicrobial regimens (22, 46). Despite their pathogenicity, enterococci constitute a major component of the microflora of artisanal cheeses produced in Europe and are considered to play an important role in ripening and aroma development (20, 67). Additionally, enterococci are used as probiotics to improve the microbial balance of the intestine and to treat gastroenteritis in humans and animals (2, 43). These bacteria probably now represent the greatest risk to human health of any bacterial species currently used for these purposes (12, 21). Additional general features of these organisms are hallmarks of their biology and may also contribute to their pathogenicity. Enterococci are distinguished for their ability to grow in 6.5% NaCl or at temperatures ranging from 10 to 45°C and to tolerate acidic and alkaline growth conditions. These observations raise the question of how enterococcal physiology has evolved to allow the organisms to sense environmental changes and respond to the various stimuli with adaptive behavior. Monitoring and adapting to changing environmental conditions is the key function of bacterial signal transduction, which is generally carried out by the so-called two-component systems. Two-component signal transduction systems have evolved to allow cells to monitor their environment and respond appropriately to a wide variety of stimuli, including nutrient deprivation, chemical changes, host-pathogen interaction, osmotic shock, and other stresses (6, 9, 28, 30, 57). While studies of enterococci have identified some general stress proteins (5, 18, 19, 24), a global view of the enterococcal signal transduction mechanisms has not been gained. The soon-to-be-completed sequences of the Enterococcus faecalis (strain V583) (The Institute for Genomic Research [TIGR]; www.tigr.org) and Enterococcus faecium (strain TX0016) (Human Genome Sequencing Center, Baylor College of Medicine) genomes will be invaluable tools to exploit in the effort to gain a better understanding of the physiology of these organisms and address the increasing threat they pose to human health.