Abstract
The pathogen Vibrio cholerae has multiple iron acquisition systems which allow bacteria to exploit a variety of iron sources across the different environments on which it thrives. The expression of such iron uptake systems is highly regulated, mainly by the master iron homeostasis regulator Fur but also by other mechanisms. Recently, we documented that the expression of many of the iron-responsive genes is also modulated by riboflavin. Among them, the open reading frame VCA0231, repressed both by riboflavin and iron, encodes a putative transcriptional regulator of the AraC/XylS family. Nonetheless, the genes or functions affected by this factor are unknown. In the present study, a series of in silico analyses was performed in order to identify the putative functions associated with the product of VCA0231. The STRING database predicted many iron uptake genes as functional partners for the product of VCA0231. In addition, a genomic neighborhood analysis with the Enzyme Function Initiative tools detected many Pfam families involved in iron homeostasis genetically associated with VCA0231. Moreover, a phylogenetic tree showed that other AraC/XylS members known to regulate siderophore utilization in bacteria clustered together and the product of VCA0231 localized in this cluster. This suggested that the product of VCA0231, here named IurV, is involved in the regulation of iron uptake processes. RNAseq was performed to determine the transcriptional effects of a deletion in VCA0231. A total of 52 genes were overexpressed and 21 genes were downregulated in response to the iurV deletion. Among these, several iron uptake genes and other iron homeostasis-related genes were found. Six gene ontology (GO) functional terms were enriched in the upregulated genes, of which five were related to iron metabolism. The regulatory pattern observed in the transcriptomics of a subset of genes was independently confirmed by quantitative real time PCR analysis. The results indicate that IurV is a novel regulator of the AraC/XylS family involved in the repression of iron uptake genes. Whether this effect is direct or indirect remains to be determined.
Highlights
V. cholerae is the causative agent of cholera, a pandemic disease characterized by acute watery diarrhea
Six are proteins involved in iron acquisition: FhuA and ViuA, which are siderophore receptors, VC1579 and VibB, two siderophore biosynthetic proteins, TonB, required for the ATP hydrolysis-driven energization of various iron uptake systems, and IrgB, an activator of the expression of the IrgA enterobactin receptor
The results suggest that AraC/XylS regulators involved in iron acquisition tend to form a cluster, as described for those with other functions
Summary
V. cholerae is the causative agent of cholera, a pandemic disease characterized by acute watery diarrhea. This bacterium causes around 4.3 million cholera cases leading to 143,000 deaths globally. Cholera epidemics are caused by a narrow group of strains belonging mainly to serogroups O1 and O139, which conserve the CT genes [3]. It has been postulated that global warming is an important factor for the increase in cholera cases worldwide [6]. All these factors make the study of the physiology of
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