Enterococcus faecalis (E. faecalis) is a commensal bacterium that causes various infections in surgical sites, the urinary tract, and blood. The bacterium is becoming a significant concern because it tends to affect the elderly population, which has a high prevalence of undiagnosed degenerative valvular disease and is often subjected to invasive procedures and implanted medical devices. The bacterium’s actions are influenced by specific characteristics like pili activity and biofilm formation. This resistance significantly impedes the effectiveness of numerous antibiotic therapies, particularly in cases of endocarditis.
Surgery is necessary for 40–50% of patients with IE [82]. Prior to the introduction of valve-repair procedures, valve replacement was the favoured option for severe valve regurgitation due to the likelihood of IE recurrence [71,83]. Valve replacement may be preferred in specific circumstances, including cases of advanced age, or when a combined or complex surgical procedure is required, involving complete tissue removal in cases of PVE. It may also be recommended in instances of extensive and harmful NVE when infectious fields encompass a significant portion of the damaged heart [24,71,82,84,85,86,87,88,89,90]. The latest treatments employ transcatheter-valve therapy (TVT) to treat structural heart disease, which has demonstrated itself as a secure and useful technique for many patients. However, it is preferable to limit its use to elderly patients with coexisting medical conditions.
The accomplishment of valve surgery for IE is based on four general principles. First, surgical procedures must ensure the complete removal of infectious vegetations, followed by the repair or replacement of one or more heart valves. Secondly, the full integrity of the cardiac structures should be restored. Thirdly, to prevent the relapse of infection, complete debridement of the infected tissue should be performed. Valve replacement with allogeneic or autologous tissue is recommended to restore full cardiac function. Finally, if a surgeon performs a valve repair, they must ensure that there is no more than a trace of mild valve regurgitation after completing the repair [65,71,83,84,85,86,87,88,89,90].
It is highly recommended to include molecular biology knowledge in conjunction with microbiology in the shared decision-making process alongside microbiological specialists. Intravenous combination therapy is generally preferred over monotherapy to minimise resistance and offer antimicrobial synergy [130]. Currently, there is encouraging laboratory data but limited clinical evidence to support the use of combination beta-lactam therapy for this indication. Further research is needed to determine the potential benefits of combining beta-lactam therapy contrasted with monotherapy to treat Gram-positive blood infections. Nonetheless, in cases of bacteremia unresponsive to standard antibiotic treatment, combining therapy may be advantageous [130]. The only exceptions are S. aureus and E. faecalis, as they are vulnerable to methicillin. Other treatment options for infections that have become resistant to vancomycin are obtainable, including linezolid, tigecycline, and daptomycin [131,132].
Given the rise in antibiotic resistance, there has been a growing interest in microbiological research that focuses on using bacterial factors as immunotherapeutic targets. This decision is based on the fact that bacterial factors play a significant role in an organism’s ability to colonise, infect, and ultimately cause disease [28]. MSCRAMMs have received significant attention recently due to their widespread presence and unique ability to promote the initiation of infections, including endocarditis [33], in both traditional and opportunistic pathogens [28,137]. Their central role in these processes is of particular interest. Unfortunately, complications have been identified in isolating and defining MSCRAMM from E. faecalis, which has yielded limited success due to this microorganism’s lack of adherence to ECM proteins in laboratory growth conditions [34,135]. This stands in contrast to its relatives, such as staphylococci and streptococci, which exhibit enhanced aggression.
To overcome this challenge, Sillanpa and colleagues utilised a bioinformatics method to identify multiple proteins that predict MSCRAMM-like structures [29]. By evaluating their reactivity with sera from E. faecalis-infected patients, the researchers concluded that some of these predicted proteins are indeed expressed by E. faecalis during infection. In particular, the study conducted by Sillanpa and colleagues [29], which examined antibodies in the sera of patients with E. faecalis endocarditis, identified nine recombinant forms of proteins anchored to the cell wall of E. faecalis. The authors noted three genes and a Sortase C (SrtC) gene, associated with sortase, which were expressed in vivo.
Research has shown that Enterococcus faecalis virulence is enhanced by cell-wall-linked proteins, such as sortase-mediated endocarditis and biofilm-linked pilus (Ebp), which play a crucial role in biofilm formation both in vitro and in vivo. Furthermore, a substantial body of contemporary literature has reported a rise in multi-drug resistance in the fight against Enterococcus faecalis infections. The creation of biofilms is a particular concern because it not only has the potential to protect drug-resistant organisms from antibiotics and opsonophagocytosis, but it can also increase horizontal gene transfer [34,138]. Previous studies on E. faecalis have demonstrated that various factors can significantly reduce the density of biofilms [55,56,57,58,59]. Disruption of esp, which encodes the surface protein of Enterococci in certain strains, promotes the latter. This promotion is facilitated by various factors including the fsr 2-component system, gelE which encodes for gelatinase, the Epa gene cluster which encodes for the polysaccharide Epa, and finally by atn which encodes for an autolysin or bopD sugar-binding transcriptional regulator [55,56,57,58,59].
This entry is adapted from the peer-reviewed paper 10.3390/microorganisms11102604