Transition metals and Enterococcus faecalis: Homeostasis, virulence and perspectives

Abstract

Enterococcus faecalis, a Gram-positive bacterium, is known to be a key player in several chronic infections as well as nosocomial, heart valve, urinary tract, surgical wound, and dental root canal infections. The capability to sense different transition metal levels and tune its response accordingly endows it with the potential to thrive and cause infections in several host niches. Over the past decade, our knowledge of how transition metals play a critical role in maintaining homeostasis of E. faecalis has improved significantly. The aim of this review is to elucidate the roles of metals such as iron, manganese, zinc, and copper in the physiology, metabolism, and pathogenicity of E. faecalis. These essential micronutrients contribute to energy production, redox stress response, expression of virulence determinants, and cooperation in polymicrobial communities. The review also highlights metal homeostasis systems in E. faecalis, which respond to fluctuations in extracellular metal levels, and regulate the intracellular metal content. Regulation of intracellular metallome secures the tolerance of E. faecalis to oxidative stress and host-mediated metal sequestration strategies. Therapeutic interventions which deprive E. faecalis of its essential metal requirements or disrupt its homeostatic control have been proposed to combat E. faecalis infections.

Gliotoxin-mediated bacterial growth inhibition is caused by specific metal ion depletion

“…Although next generation antibiotics, vaccination and bacteriophage therapies have been proposed to overcome AMR, the problem is still growing, which means that additional strategies must be considered to either identify new bacterial drug targets or augment existing antibiotic therapies 3 – 6 . Herein work is presented on the effects of the fungal non-ribosomal peptide, gliotoxin (GT), on ESKAPE pathogens and Enterococcus faecalis , selected due to the worrying trend of antibiotic resistant isolates that have been found for this bacterial species, often leading to nosocomial infections 7 , 8 .…”

The Potential Clinical Applications of a Microfluidic Lab-on-a-Chip for the Identification and Antibiotic Susceptibility Testing of Enterococcus faecalis-Associated Endodontic Infections: A Systematic Review

“…Operating as an opportunistic pathogen, E. faecalis seizes the opportunity to cause severe diseases, occasionally leading to fatal outcomes, especially when the host's immune defences are compromised [2]. Moreover, it is involved in the development of chronic infections like infective endocarditis, abdominal infections, urinary tract infections, surgical wound infections, bacteraemia, and endodontic infections [3].…”