ArticlePLoS pathogens2018
Manganese acquisition is essential for virulence of Enterococcus faecalis.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 83 citations in OpenAlex.
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- A Novel Heme-Degrading Enzyme that Regulates Heme and Iron Homeostasis and Promotes Virulence inbioRxiv : the preprint server for biology · 2025Article
- Metals in the gut: microbial strategies to overcome nutritional immunity in the intestinal tract.Metallomics : integrated biometal science · 2024Review
- Manganese uptake by MtsABC contributes to the pathogenesis of human pathogen group A streptococcus by resisting host nutritional immune defenses.Infection and immunity · 2024Article
- Enhanced vegetable production in hydroponic systems using decontamination of closed circulating fluid.Scientific reports · 2024Article
- Trivalent immunization with metal-binding proteins confers protection against enterococci in a mouse infection model.FEMS microbes · 2024Article
- Slc11 Synapomorphy: A Conserved 3D Framework Articulating Carrier Conformation Switch.International journal of molecular sciences · 2023Article
- Identification of Multiple Iron Uptake Mechanisms in Enterococcus faecalis and Their Relationship to Virulence.Infection and immunity · 2023Article
- The AdcACB/AdcAII system is essential for zinc homeostasis and an important contributor ofVirulence · 2022Article
- PerR-Regulated Manganese Import Contributes to Oxidative Stress Defense in Streptococcus suis.Applied and environmental microbiology · 2022Article
- Contribution of a ZIP-family protein to manganese uptake and infective endocarditis virulence in Streptococcus sanguinis.Molecular microbiology · 2022Article
- Methods for Using the Galleria mellonella Invertebrate Model to Probe Enterococcus faecalis Pathogenicity.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Nramp: Deprive and conquer?Frontiers in cell and developmental biology · 2022Article
- Regulation and distinct physiological roles of manganese in bacteria.FEMS microbiology reviews · 2021Review
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8 authors at 4 institutions in 1 country.
Funding
Abstract
Manganese (Mn) is an essential micronutrient that is not readily available to pathogens during infection due to an active host defense mechanism known as nutritional immunity. To overcome this nutrient restriction, bacteria utilize high-affinity transporters that allow them to compete with host metal-binding proteins. Despite the established role of Mn in bacterial pathogenesis, little is known about the relevance of Mn in the pathophysiology of E. faecalis. Here, we identified and characterized the major Mn acquisition systems of E. faecalis. We discovered that the ABC-type permease EfaCBA and two Nramp-type transporters, named MntH1 and MntH2, work collectively to promote cell growth under Mn-restricted conditions. The simultaneous inactivation of EfaCBA, MntH1 and MntH2 (ΔefaΔmntH1ΔmntH2 strain) led to drastic reductions (>95%) in cellular Mn content, severe growth defects in body fluids (serum and urine) ex vivo, significant loss of virulence in Galleria mellonella, and virtually complete loss of virulence in rabbit endocarditis and murine catheter-associated urinary tract infection (CAUTI) models. Despite the functional redundancy of EfaCBA, MntH1 and MntH2 under in vitro or ex vivo conditions and in the invertebrate model, dual inactivation of efaCBA and mntH2 (ΔefaΔmntH2 strain) was sufficient to prompt maximal sensitivity to calprotectin, a Mn- and Zn-chelating host antimicrobial protein, and for the loss of virulence in mammalian models. Interestingly, EfaCBA appears to play a prominent role during systemic infection, whereas MntH2 was more important during CAUTI. The different roles of EfaCBA and MntH2 in these sites could be attributed, at least in part, to the differential expression of efaA and mntH2 in cells isolated from hearts or from bladders. Collectively, this study demonstrates that Mn acquisition is essential for the pathogenesis of E. faecalis and validates Mn uptake systems as promising targets for the development of new antimicrobials.
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