Utilization of transferrin-bound iron by Listeria monocytogenes

Hartford, T.

doi:10.1016/0378-1097(93)90561-f

Cited by 19 publications

(18 citation statements)

References 11 publications

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“…Another system involves an extracellular ferric iron reductase, which uses as a substrate naturally occurring iron-loaded catecholamines and siderophores (2,21,111,112,133). The third system may involve a bacterial cell surface-located transferrinbinding protein (263), although the existence of such a mechanism has been questioned (43). No experimental evidence is currently available on the contribution of these iron uptake systems to the pathogenesis of L. monocytogenes infection.…”

Section: Other Virulence Factorsmentioning

confidence: 99%

ListeriaPathogenesis and Molecular Virulence Determinants

et al. 2001

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The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal indivuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research

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Section: Other Virulence Factorsmentioning

confidence: 99%

ListeriaPathogenesis and Molecular Virulence Determinants

et al. 2001

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“…Following infection, the mammalian host has several strategies to defend itself against invading microbes. One of these is to decrease the amount of available iron by binding free extracellular iron to iron-binding proteins such as transferrin and lactoferrin (Hartford et al, 1993). Iron is essential for most bacterial species, as it functions as a co-factor in different proteins, is involved in various cellular functions, and is a major environmental stimulus capable of regulating virulence gene expression in many bacterial pathogens (Adams et al, bind iron (Bozzi et al, 1997;Grant et al, 1998;Ilari et al, 2000;Tonello et al, 1999;Yamamoto et al, 2002;Zhao et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The Dps-like protein Fri of Listeria monocytogenes promotes stress tolerance and intracellular multiplication in macrophage-like cells

Olsen¹,

Larsen²,

Gahan

et al. 2005

Microbiology

103

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Members of the ferritin-like Dps protein family are found in a number of bacterial species, where they demonstrate the potential to bind iron, and have been implicated in tolerance to oxidative stress. In this study of the food-borne pathogen Listeria monocytogenes, the fri gene encoding a Dps homologue was deleted, and, compared to wild-type cells, it was found that the resulting mutant was less resistant to hydrogen peroxide, and demonstrated reduced survival following long-term (7–11 days) incubation in laboratory media. In view of this, it is shown that fri gene expression is controlled by the hydrogen peroxide regulator PerR, as well as the general stress sigma factor σ B. When fri mutant cells were transferred to iron-limiting conditions, growth was retarded relative to wild-type cells, indicating that Fri may be required for iron storage. This notion is supported by the observation that the L. monocytogenes genome appears not to encode other ferritin-like proteins. Given the role of Fri in resistance to oxidative stress, and growth under iron-limiting conditions, the ability of the fri mutant to infect mice was examined. When injected by the intraperitoneal route, the fri mutant demonstrated a reduced capacity to proliferate in the organs of infected mice relative to the wild-type, whereas when the bacteria were supplied intravenously this effect was mitigated. In addition, the mutant was impaired in its ability to survive and grow in J774.A1 mouse macrophage cells. Thus, the data suggest that Fri contributes to the ability of L. monocytogenes to survive in environments where oxidative stress and low iron availability may impede bacterial proliferation.

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“…Similar to Streptococcus pneumoniae, no siderophore synthesis has been detected in L. monocytogenes, and whole-genome sequence data of L. monocytogenes indicate that such genes are absent in this bacterium (Cowart & Foster, 1985;Tai et al, 1993;Glaser et al, 2001). It has been reported that L. monocytogenes can utilize transferrin, ferritin, lactoferrin, haemin, catecholamine, and siderophores produced by other bacteria in the environment, as sources of iron (Hartford et al, 1993;Jin et al, 2006; Mikael et al, 2002; Newton et al, 2005;Simon et al, 1995). Additionally, extracellular iron reductase activity has also been reported in this bacterium (Barchini & Cowart, 1996;Coulanges et al, 1997Coulanges et al, , 1998Cowart & Foster, 1985;Deneer et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of the Fur protein of Listeria monocytogenes

et al. 2007

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Iron is essential for the survival of almost all organisms, although excess iron can result in the generation of free radicals which are toxic to cells. To avoid the toxic effects of free radicals, the concentration of intracellular iron is generally regulated by the ferric uptake regulator Fur in bacteria. The 150 aa fur ORF from Listeria monocytogenes was cloned into pRSETa, and the His-tagged fusion protein was purified by nickel affinity column chromatography. DNA binding activity of this protein was studied by an electrophoretic mobility shift assay using the end-labelled promoters P fhuDC and P fur . The results showed a decrease in migration for both promoter DNAs in the presence of the Fur protein, and the change in migration was competitively inhibited with an excess of the same unlabelled promoters. No shift in migration was observed when a similar assay was performed using non-specific end-labelled DNA. The assay showed that binding of Fur to P fur or P fhuDC was independent of iron or manganese ions, and was not inhibited in the presence of 2 mM EDTA. Inductively coupled plasma MS of the Fur protein showed no iron or manganese, but 0.48 mole zinc per mole protein was detected. A DNase I protection assay revealed that Fur specifically bound to and protected a 19 bp consensus Fur box sequence located in the promoters of fur and fhuDC. There was no requirement for iron or manganese in this assay also. However, Northern blot analysis showed an increase in fur transcription under iron-restricted compared to high-level conditions. Thus, the study suggests that under in vitro conditions, the affinity of the Fur protein for the 19 bp Fur box sequence does not require iron, but iron availability regulates fur transcription in vivo. Thus, the regulation by Fur in this intracellular pathogen may be dependent on either the structure of the DNA binding domain or other intracellular factors yet to be identified. INTRODUCTIONIron is an essential element for most bacteria, as many enzymes involved in cellular metabolism require iron as a co-factor (Griffiths, 1999). In bacteria, the level of iron determines the expression of several virulence factors (Braun, 2005;Litwin & Calderwood, 1993 (Gutteridge et al., 1982;Imlay et al., 1988). Several proteins, such as albumin, ferritin, lactoferrin and transferrin, present in humans, reduce this toxicity by sequestering free Fe 2+ and oxidizing it to insoluble Fe 3+ , which is not readily available to support bacterial growth (Weinberg, 1978). Hence, the survival and growth of bacteria during infection depends on their ability to interact with and acquire iron from the host. Bacteria have evolved several mechanisms to help utilization of host iron-bound compounds directly, or to separate iron from other host sources. Under iron-limiting conditions, most bacteria produce siderophores, which can solubilize iron in the environment and present it to specific receptors for transport into the bacteria. Several reports have indicated that Gram-positive pathogenic bacteria can utili...

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Utilization of transferrin-bound iron by Listeria monocytogenes

Cited by 19 publications

References 11 publications

ListeriaPathogenesis and Molecular Virulence Determinants

ListeriaPathogenesis and Molecular Virulence Determinants

The Dps-like protein Fri of Listeria monocytogenes promotes stress tolerance and intracellular multiplication in macrophage-like cells

Molecular characterization of the Fur protein of Listeria monocytogenes

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