Transcriptomic response of Enterococcus faecalis to iron excess

Abstract

Iron is an essential nutrient for sustaining bacterial growth; however, little is known about the molecular mechanisms that govern gene expression during the homeostatic response to iron availability. In this study we analyzed the global transcriptional response of Enterococcus faecalis to a non-toxic iron excess in order to identify the set of genes that respond to an increment of intracellular iron. Our results showed an up-regulation of transcriptional regulators of the Fur family (PerR and ZurR), the cation efflux family (CzcD) and ferredoxin, while proton-dependent Mn/Fe (MntH) transporters and the universal stress protein (UspA) were down-regulated. This indicated that E. faecalis was able to activate a transcriptional response while growing in the presence of an excess of non-toxic iron, assuring the maintenance of iron homeostasis. Gene expression analysis of E. faecalis treated with H(2)O(2) indicated that a fraction of the transcriptional changes induced by iron appears to be mediated by oxidative stress. A comparison of our transcriptomic data with a recently reported set of differentially expressed genes in E. faecalis grown in blood, revealed an important fraction of common genes. In particular, genes associated to oxidative stress were up-regulated in both conditions, while genes encoding the iron uptake system (feo and ycl operons) were up-regulated when cells were grown in blood. This suggested that blood cultures mimic an iron deficit, and was corroborated by measuring feo and ycl expression in E. faecalis treated with the iron chelating agent 2,2-dipyridil. In summary, our group identified an adaptive transcriptional mechanism in response to metal ion stress in E. faecalis, providing a foundation for future in-depth functional studies of the iron-activated regulatory network.

Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci

“…Seven of these genes have previously been implicated in metal stress response in E. faecalis; specifically, they are upregulated in response to zinc (47,48). In addition, the ortholog of EFTG_01192 in E. faecalis V583, referred to as EF1057, is downregulated in response to iron chloride excess (49). Orthologs of another predicted transport system, encoded by EFTG_02287-02288 in E. faecium 1,231,410 and EF2226-EF2227 in E. faecalis V583, were upregulated in Fst toxin-treated E. faecalis OG1X (39), indicating overlap with the extracytoplasmic stress response.…”

Regulating the Intersection of Metabolism and Pathogenesis in Gram-positive Bacteria

“…Whereas the activity of phosphofructokinase is independent of iron, phosphofructokinase activity and carbon flux through glycolysis are nonetheless affected by growth in iron-limited conditions. Two possible explanations can be considered: First, variations in the availability of iron alter transcription of the phosphofructokinase gene in Mycobacterium smegmatis , Enterococcus faecalis , and S. aureus (8–10). Second, some bacteria, when cultivated in an iron-limiting medium, accumulate citric acid in the cytosol and the culture medium due to a metabolic block in the Krebs cycle at aconitase (2, 11–13).…”

Current status and emerging role of glutathione in food grade lactic acid bacteria

“…GshR activity (besides other antioxidative enzymes) helps S. thermophilus to adapt several treatments during industrial processing [30]. Similarly, E. faecalis and E. faecium was also reported to produce high GSH in rich medium [28,31] as well as in CDM [32] and is also able to regenerate the reduced form by glutathione reductase (GshR) activity under oxidative stress [33]. Our analysis showed the presence of transport protein CydDC as well as glutathione biosynthesis fusion protein GshF in E. faecalis genome.…”

“…Iron supplementation in the medium presents E. faecalis cells with oxidative stress with a consequential decrease in cellular glutathione content [31]. Profiling of genes overexpressed in Lb.…”