Enterococcal-host interactions in the gastrointestinal tract and beyond

The gastrointestinal tract (GIT) is typically considered the natural niche of enterococci. However, these bacteria also inhabit extraintestinal tissues, where they can disrupt organ physiology and cause life-threatening infections. Here, we discuss how enterococci, primarily Enterococcus faecalis, interact with the intestine and other host anatomical locations such as the oral cavity, heart, liver, kidney, and vaginal tract. The metabolic flexibility of these bacteria allows them to quickly adapt to new environments, promoting their persistence in diverse tissues. In transitioning from commensals to pathogens, enterococci must overcome harsh conditions such as nutrient competition, exposure to antimicrobials, and immune pressure. Therefore, enterococci have evolved multiple mechanisms to adhere, colonize, persist, and endure these challenges in the host. This review provides a comprehensive overview of how enterococci interact with diverse host cells and tissues across multiple organ systems, highlighting the key molecular pathways that mediate enterococcal adaptation, persistence, and pathogenic behavior.