The vast majority of enterococci, including species that are major agents of nosocomial infection, are peaceful inhabitants of the gastrointestinal (GI) tracts of animals that range from insects to humans. However, situations arise in which enterococci can cause serious disease. The era of modern medicine has created circumstances that facilitate the pathogenic behavior of these microbes in the following ways. First, the use, and arguable overuse, of antibiotics has selected for bacteria that are resistant to these medicines. Even though enterococci may not be as inherently virulent as some other bacterial pathogens, they are facile at collecting and exchanging antibiotic resistance determinants, in addition to being naturally resistant to many antibitoics. Such properties give enterococci a selective advantage in environments with heavy antibiotic usage, such as the hospital, and may allow them to out-compete other species that would normally keep them in check. Another factor is the increasing susceptible population of immunocompromised individuals, which includes the elderly, solid organ and bone marrow transplant patients, and cancer patients. The action of the immune system likely contributes to the commensal balance, and a severely weakened defense system may be unable to keep these species in check. Finally, there are genetic factors that contribute to the ability of enterococci to survive and cause infection in a host environment, which are defined as virulence determinants for the purpose of this discussion. Some of these factors are part of the core genome, while others are traits that can be acquired and shared. Much work has been done over the last 20 years to identify these virulence determinants, and to characterize their mechanisms of action, which is is the main focus of this chapter.
Animal models have made critical contributions to our understanding of the pathogenesis of enterococcal infection. A number of advances recently have been made that allow for new and more facile models to be employed in these studies. However, since the motivation behind a given study usually relates to some aspect of human infection, it is important to understand the parallels and limitations of each model, in order to know the extent to which the results can be extrapolated to humans.