Role of iron in regulation of virulence genes

Abstract

The abilities of bacterial pathogens to adapt to the environment within the host are essential to their virulence. Microorganisms have adapted to the iron limitation present in mammalian hosts by evolving diverse mechanisms for the assimilation of iron sufficient for growth. In addition, many bacterial pathogens have used the low concentration of iron present in the host as an important signal to enhance the expression of a wide variety of bacterial toxins and other virulence determinants. The molecular basis of coordinate regulation by iron has been most thoroughly studied in Escherichia coli. In this organism, coordinate regulation of gene expression by iron depends on the regulatory gene, fur. Regulation of gene expression by iron in a number of pathogenic organisms is coordinated by proteins homologous to the Fur protein of E. coli. Additional regulatory proteins may be superimposed on the Fur repressor to provide the fine-tuning necessary for the precise regulation of individual virulence genes in response to iron and other environmental signals. Studies of the mechanisms of regulation of iron acquisition systems and virulence determinants by iron should lead to a better understanding of the adaptive response of bacteria to the low-iron environment of the host and its importance in virulence.

Genomic versatility and functional variation between two dominant heterotrophic symbionts of deep-sea Osedax worms

“…Iron uptake, which is discussed in more detail later, is also potentially accomplished via three separate mechanisms in each symbiont, including ABC transport of ferric iron and heme by both symbionts, as well as hemin uptake by the Rs1 symbiont and siderophoremediated iron uptake in symbiont Rs2 (Table 3). All of these genes were identified along operons (3-8 kb), on large contigs (11-90 kb), and included the presence of the Fur gene, which mediates the transcriptional regulation, via its protein product, of iron-related genes (Litwin and Calderwood, 1993). Similarly, only 2 of 17 close relatives examined possessed all three distinct mechanisms for iron uptake.…”

Environmentally regulated genes of Streptococcus suis: identification by the use of iron-restricted conditions in vitro and by experimental infection of piglets The GenBank accession numbers for the sequences determined in this work are AF302190–AF302207 (iri genes) and AF303226–303247 (ivs genes).

“…Examples are signature-tagged mutagenesis (STM) and in vivo expression technology (IVET ; Mahan et al, 1993Mahan et al, , 1995Camilli & Mekalanos, 1995 ;Hensel et al, 1995 ;Mei et al, 1997 ;Young & Miller, 1997 ;Chiang & Mekalanos, 1998 ;Coulter et al, 1998 ;Lowe et al, 1998 ;Polissi et al, 1998 ;Camacho et al, 1999 ;Darwin & Miller, 1999 ;Edelstein et al, 1999 ;Fuller et al, 1999 ;Zhao et al, 1999). In addition, important virulence proteins could also be identified by the selection of genes specifically expressed under conditions mimicking in vivo conditions, for example by growth under ironrestricted conditions (Litwin & Calderwood, 1993 ;Martinez et al, 1990). The aim of the present work was to identify virulence genes of Strep.…”

Uptake of iron from different compounds by enteroinvasive Escherichia coli

“…The majority of iron is found intracellularly as mioglobin, ferritin, hemosiderin and hemoglobin (12). The trace quantities of extracellular iron is bound to the glycoproteins transferrin, in the blood, and lactoferrin, in secretions and mucosal surfaces (1,19).…”

“…Iron is an essential element for living organisms. This ion is a very versatile biocatalyst (12) and this characteristic is responsible for its involvement in so many essential processes for the cells, such as breathing and ribonucleotide synthesis. Despite its importance, iron is not readily available in aquatic or terrestrial environments and in animal hosts (8).…”