Enterococcus faecalis

Modern hospitals and antibiotic treatment alone did not create all the antibiotic resistant strains of bacteria we see today. Instead, selection pressures from before widespread use of antibiotics influenced some of them to develop, new research has discovered.

By using analytical and sequencing technology that has only been developed in recent years, scientists from Wellcome Sanger Institute, University of Oslo and University of Cambridge have created an evolutionary timeline of the bacterium, Enterococcus faecalis, which is a common bacterium that can cause antibiotic resistant infections in hospitals.

The results, published today (March 9th, 2021) in Nature Communications show that this bacterium has the ability to adapt very quickly to selection pressures, such as the use of chemicals in farming as well as the development of new medications, which have caused different strains of the same bacterium to be found in many places worldwide, from the majority of people’s guts to many wild birds. As it is so widespread, the researchers suggest people should be screened for this type of bacteria when entering the hospital, in the same way they are for other superbugs, to help reduce the possibility of developing and spreading infection within healthcare.

Enterococcus faecalis is a common bacterium that, in most people, is found in the intestinal tract and doesn’t cause harm to the host. However, if someone is immunocompromised and this bacterium gets into the bloodstream, it can cause a serious infection.

In hospitals, it is more common to find antibiotic resistant strains of E. faecalis and it was initially thought that the wide use of antibiotics and other antibacterial control measures in modern hospitals caused these strains to develop.

In a new study, scientists from Wellcome Sanger Institute, University of Oslo and University of Cambridge analysed around 2000 samples of E. faecalis from 1936 to present day using blood stream isolates from patients and stool samples from animals and healthy humans.

By sequencing the genome (including chromosomes and plasmids) using technology from Oxford Nanopore, the team mapped the evolutionary journey of the bacterium and created a timeline of when and where different strains developed, including those nowadays found to be resistant to antibiotics. They found that antibiotic resistant strains developed earlier than previously thought, before the widespread use of antibiotics, and therefore it was not antibiotic use alone that caused these to emerge.

Researchers found that agricultural and early medical practices, such as the use of arsenic and mercury, influenced the evolution of some of the strains we see now. In addition to this, strains similar to the antibiotic resistant variants we see in hospitals now were found in wild birds. This shows how adaptable and flexible this species of bacterium is at evolving into new strains in the face of different adversity.

Professor Jukka Corander, co-lead author and Associate Faculty member at the Wellcome Sanger Institute, said: “This is the first time we have been able to map out the full evolution of E. faecalis from samples up to 85 years old, which enables us to see the detailed effect of human lifestyles, agriculture and medicines on the development of different bacterial strains. Having the full timeline of evolutionary changes would not have been possible without analytical and sequencing techniques that can be found at the Sanger Institute.” Read more...

Wikipedia

Enterococcus faecalis – formerly classified as part of the group D Streptococcus system – is a Gram-positive, commensal bacterium inhabiting the gastrointestinal tracts of humans and other mammals. Like other species in the genus Enterococcus, E. faecalis can cause life-threatening infections in humans, especially in the nosocomial (hospital) environment, where the naturally high levels of antibiotic resistance found in E. faecalis contribute to its pathogenicity. E. faecalis has been frequently found in root canal-treated teeth in prevalence values ranging from 30% to 90% of the cases. Root canal-treated teeth are about nine times more likely to harbor E. faecalis than cases of primary infections.

Physiology

E. faecalis is a nonmotile microbe; it ferments glucose without gas production, and does not produce a catalase reaction with hydrogen peroxide. It can produce a pseudocatalase reaction if grown on blood agar. The reaction is usually weak. It produces a reduction of litmus milk, but does not liquefy gelatin. It shows consistent growth throughout nutrient broth which is consistent with being an aerotolerant anaerobe. They catabolize a variety of energy sources including glycerol, lactate, malate, citrate, arginine, agmatine, and many keto acids. Enterococci survive very harsh environments including extremely alkaline pH (9.6) and salt concentrations. They resist bile salts, detergents, heavy metals, ethanol, azide, and desiccation. They can grow in the range of 10 to 45 °C and survive at temperatures of 60 °C for 30 min.^[4]

Pathogenesis

E. faecalis can cause endocarditis and septicemia, urinary tract infections, meningitis, and other infections in humans.^[5][6] Several virulence factors are thought to contribute to E. faecalis infections. A plasmid-encoded hemolysin, called the cytolysin, is important for pathogenesis in animal models of infection, and the cytolysin in combination with high-level gentamicin resistance is associated with a five-fold increase in risk of death in human bacteremia patients. A plasmid-encoded factor called "aggregation substance" is also important for virulence in animal models of infection.

This is a Gram stain for Enterococcus faecalis under 1000 magnification (bright field microscopy)

Antibacterial resistance

E. faecalis is resistant to many commonly used antimicrobial agents (aminoglycosides, aztreonam, cephalosporins, clindamycin, the semisynthetic penicillins nafcillin and oxacillin, and trimethoprim-sulfamethoxazole).^[citation ^needed] Resistance to vancomycin in E. faecalis is becoming more common. Treatment options for vancomycin-resistant E. faecalis include nitrofurantoin (in the case of uncomplicated UTIs), linezolid, and daptomycin, although ampicillin is preferred if the bacteria are susceptible. Quinupristin/dalfopristin can be used to treat Enterococcus faecium but not E. faecalis.

In root canal treatments, NaOCl and chlorhexidine (CHX) are used to fight E. faecalis before isolating the canal. However, recent studies determined that NaOCl or CHX showed low ability to eliminate E. faecalis.

Survival and virulence factors

Endures prolonged periods of nutritional deprivation
Binds to dentin and proficiently invades dentinal tubules
Alters host responses
Suppresses the action of lymphocytes
Possesses lytic enzymes, cytolysin, aggregation substance,pheromones, and lipoteichoic acid
Utilizes serum as a nutritional source
Resists intracanal medicaments (i.e. Ca(OH)₂)
- Maintains pH homeostasis
- Properties of dentin lessen the effect of calcium hydroxide

Competes with other cells
Forms a biofilm

Historical

Prior to 1984, enterococci were members of the genus Streptococcus; thus, E. faecalis was known as Streptococcus faecalis.

In 2013, a combination of cold denaturation and NMR spectroscopy was used to show detailed insights into the unfolding of the E. faecalis homodimeric repressor protein CylR2.

Genome structure

The E. faecalis genome consists of 3.22 million base pairs with 3,113 protein-coding genes.

SMALL RNA

Bacterial small RNAs play important roles in many cellular processes. 11 small RNAs have been experimentally characterised in E. faecalis V583 and detected in various growth phases.