title: 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.
authors.affiliation: Laboratorio de Bioinformática y Expresión Génica, INTA, Universidad de Chile, El Líbano 5524, Macul, Santiago, Chile. glopez@inta.uchile.cl
authors.forename: Guadalupe
authors.initials: G
authors.lastname: López
authors.forename: Mauricio
authors.initials: M
authors.lastname: Latorre
authors.forename: Angélica
authors.initials: A
authors.lastname: Reyes-Jara
authors.forename: Verónica
authors.initials: V
authors.lastname: Cambiazo
authors.forename: Mauricio
authors.initials: M
authors.lastname: González
mesh_terms: D015082:2,2'-Dipyridyl / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D018384:Oxidative Stress / Q000187:drug effects; D016133:Polymerase Chain Reaction
chemical_list: D001426:Bacterial Proteins; D015082:2,2'-Dipyridyl; D006861:Hydrogen Peroxide; D007501:Iron; D005978:Glutathione