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Query: UMLS:C0004623 (bacterial infection)
 15,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence and clinical spectrum of severe bacterial infection were studied in 89 patients with thalassemia major that was diagnosed between January 1971 and March 2002. There were 20 patients with 24 episodes of severe bacterial infection, resulting in an incidence of 1.6 infections per 100 patient-years. The clinical spectrum included liver abscess (6 cases), septicemia (6 cases), soft-tissue infection (2 cases), osteomyelitis (2 cases), corneal ulcer (1 case), enteritis (1 case), and abscesses of the lung, kidney, intra-abdominal region, retropharynx, gums, and buttocks (1 case each). The leading causal microorganisms were gram-negative bacilli, especially Klebsiella pneumoniae (10 of 20 isolates). Other responsible pathogens were Pseudomonas aeruginosa (2/20), Vibrio vulnificus (2/20), Acinetobacter baumanii (1/20), Streptococcus intermidius (1/20), Yersinia enterocolitica (1/20), Staphylococcus aureus (1/20), Escherichia coli (1/20), and Salmonella species (1/20). Splenectomy and delays in the start of iron-chelating therapy were 2 independent risk factors.
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PMID:Severe bacterial infection in transfusion-dependent patients with thalassemia major. 1509 30

NRAMP1 (natural resistance-associated macrophage protein-1) and DMT1 (divalent metal-ion transporter-1) make up the SLC11 gene family of metal-ion transporters that are energized by the H(+) electrochemical gradient. Long known to confer resistance to bacterial infection, NRAMP1 functions at the phagolysosomal membrane of macrophages and neutrophils. NRAMP1 most likely contributes to macrophage antimicrobial function by extruding essential metal ions (including Mn(2+)) from the phagolysosome via H(+)/metal-ion cotransport. An alternative hypothesis in the literature proposes that NRAMP1 concentrate Fe(2+) within the phagolysosome by means of H(+)/Fe(2+) antiport, resulting in the generation of toxic free radicals. DMT1 is expressed widely and accepts as substrates a broad range of transition metal ions, among which Fe(2+) is transported with high affinity ( K(0.5) approximately 2 microM). DMT1 accounts both for the intestinal absorption of free Fe(2+) and for transferrin-associated endosomal Fe(2+) transport in erythroid precursors and many other cell types. DMT1 is up-regulated dramatically in the intestine by dietary iron restriction and, despite high serum iron levels, is not appropriately down-regulated in hereditary hemochromatosis.
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PMID:SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1. 1453 Sep 73

Oral iron is typically insufficient for the iron deficiency of hemodialysis patients. Intravenous (IV) iron is well tolerated by most patients and non-dextran-containing iron preparations are associated with few allergic reactions. However, there is the potential for an increased risk of infection with IV iron that appears to increase bacterial growth as well as inhibit the host's innate immune response to bacterial infection. Clinical studies suggest a link between iron therapy and infection. Practicing nephrologists should be aware of this issue, but should not hesitate to use IV iron in iron-deficient patients while avoiding the development of iron overload and administration of iron to patients who have active infection.
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PMID:Intravenous iron and the risk of infection in end-stage renal disease patients. 1471 13

Bacterial sepsis is the second leading cause of death among hemodialysis (HD) patients. Iron overload and intravenous iron therapy are linked to bacterial infection. This study examined iron stores, intravenous iron dosing, and bacteremic risk in HD patients. Retrospectively, 132 HD patients receiving their first course of intravenous iron were studied. Baseline laboratory values, including transferrin saturation (TSAT) value and ferritin level, were measured before initiating intravenous iron therapy. Patients were followed for up to 1 year after the initiation of iron therapy for the outcome of bacteremia by Cox proportional hazards regression analysis. Iron-replete patients (those with a TSAT value > or =20% and a ferritin level > or =100 ng/mL) had a significantly higher risk of bacteremia (hazard ratio [HR], 2.5). Venous catheter users (HR, 4.9) and those with diabetes mellitus (HR, 2.2) were also at increased risk. Modest iron storage levels may increase the risk of bacteremia among HD patients initiating intravenous iron therapy. Additional studies are needed to confirm these relationships.
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PMID:Iron storage indices: novel predictors of bacteremia in hemodialysis patients initiating intravenous iron therapy. 1509 12

We previously identified a partial Dermacentor variabilis cDNA encoding ferritin HC (HC) subunit homolog (DVFER) that was differentially upregulated in Rickettsia montanensis infected ticks (Mulenga et al., 2003a). We have used rapid amplification of cDNA ends to clone full-length DVFER cDNA and its apparent ortholog from the wood tick, D. andersoni (DAFER), both of which show high sequence similarity to vertebrate than insect ferritin. Both DVFER and DAFER contain the stem-loop structure of a putative iron responsive element in the 5' untranslated region (nucleotide positions, 16-42) and the feroxidase centre loop typical for vertebrate ferritin HC subunits. Quantitative Western and Northern blotting analyses of protein and RNA from unfed and partially fed whole tick as well as dissected tick tissues demonstrated that DVFER is constitutively and ubiquitously expressed. Based on densitometric analysis of detected protein and mRNA bands, DVFER is predominantly expressed in the midgut, and to a lesser extent in the salivary glands, ovary and fatbody. Sham treatment (mechanical injury) and Escherichia coli challenge of D. variabilis ticks stimulated statistically significant (approximately 1.5- and approximately 3.0-fold, respectively) increases in DVFER mRNA abundance over time point matched naive control ticks. These data suggest that DVFER mRNA is nonspecifically up regulated in response to mechanical injury or bacterial infection induced stress.
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PMID:Stress and transcriptional regulation of tick ferritin HC. 1527 Dec 15

The serum concentrations of two acute phase proteins (APPs), haptoglobin (Hp) and serum amyloid-A (SAA), were monitored in reindeer after challenge with endotoxin. Four adult female reindeer received either 0.1 microg/kg Escherichia coli 0111:B4 lipopolysaccharide B or saline solution intravenously. At the second challenge, the treatments were reversed. In addition to the APPs, changes in blood chemistry and rectal temperature were monitored. The endotoxin challenge caused a significant increase in SAA (peak 48 h) and a sharp decrease (8-12 h) of serum iron concentrations in all animals. The mean Hp concentration increased at 8 h and remained elevated until 48 h, but no statistically significant differences were found. This investigation demonstrates that challenge with a single-bolus dose of E. coli endotoxin can activate the acute phase response (APR) and SAA appears to be a more sensitive indicator of the APR than Hp during bacterial infection in reindeer.
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PMID:Acute phase response in reindeer after challenge with Escherichia coli endotoxin. 1532 14

Although iron is required to sustain life, its free concentration and metabolism have to be tightly regulated. This is achieved through a variety of iron-binding proteins including transferrin and ferritin. During infection, bacteria acquire much of their iron from the host by synthesizing siderophores that scavenge iron and transport it into the pathogen. We recently demonstrated that enterochelin, a bacterial catecholate siderophore, binds to the host protein lipocalin 2 (ref. 5). Here, we show that this event is pivotal in the innate immune response to bacterial infection. Upon encountering invading bacteria the Toll-like receptors on immune cells stimulate the transcription, translation and secretion of lipocalin 2; secreted lipocalin 2 then limits bacterial growth by sequestrating the iron-laden siderophore. Our finding represents a new component of the innate immune system and the acute phase response to infection.
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PMID:Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. 1560 35

Shigella flexneri, the etiologic agent of bacillary dysentery, invades epithelial cells as well as macrophages and dendritic cells and escapes into the cytosol soon after invasion. Dissection of the global gene expression profile of the bacterium in its intracellular niche is essential to fully understand the biology of Shigella infection. We have determined the complete gene expression profiles for S. flexneri infecting human epithelial HeLa cells and human macrophage-like U937 cells. Approximately one quarter of the S. flexneri genes showed significant transcriptional adaptation during infection; 929 and 1,060 genes were up- or down-regulated within HeLa cells and U937 cells, respectively. The key S. flexneri virulence genes, ipa-mxi-spa and icsA, were drastically down-regulated during intracellular growth. This theme seems to be common in bacterial infection, because the Ipa-Mxi-Spa-like type III secretion systems were also down-regulated during mammalian cell infection by Salmonella enterica serovar Typhimurium and Escherichia coli O157. The bacteria experienced restricted levels of iron, magnesium, and phosphate in both host cell types, as shown by up-regulation of the sitABCD system, the mgtA gene, and genes of the phoBR regulon. Interestingly, ydeO and other acid-induced genes were up-regulated only in U937 cells and not in HeLa cells, suggesting that the cytosol of U937 cells is acidic. Comparison with the gene expression of intracellular Salmonella serovar Typhimurium, which resides within the Salmonella-containing vacuole, indicated that S. flexneri is exposed to oxidative stress in U937 cells. This work will facilitate functional studies of hundreds of novel intracellularly regulated genes that may be important for the survival and growth strategies of Shigella in the human host.
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PMID:Transcriptional adaptation of Shigella flexneri during infection of macrophages and epithelial cells: insights into the strategies of a cytosolic bacterial pathogen. 1561 44

Siderocalin, a member of the lipocalin family of binding proteins, is found in neutrophil granules, uterine secretions, and at markedly elevated levels in serum and synovium during bacterial infection; it is also secreted from epithelial cells in response to inflammation or tumorigenesis. Identification of high-affinity ligands, bacterial catecholate-type siderophores (such as enterochelin), suggested a possible function for siderocalin: an antibacterial agent, complementing the general antimicrobial innate immune system iron-depletion strategy, sequestering iron as ferric siderophore complexes. Supporting this hypothesis, siderocalin is a potent bacteriostatic agent in vitro under iron-limiting conditions and, when knocked out, renders mice remarkably susceptible to bacterial infection. Here we show that siderocalin also binds soluble siderophores of mycobacteria, including M. tuberculosis: carboxymycobactins. Siderocalin employs a degenerate recognition mechanism to cross react with these dissimilar types of siderophores, broadening the potential utility of this innate immune defense.
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PMID:Siderocalin (Lcn 2) also binds carboxymycobactins, potentially defending against mycobacterial infections through iron sequestration. 1564 54

Bacterial resistance to antibiotics is a major threat to clinical medicine. However, natural resistance to bacterial infection, which does not depend on antibiotics, is a powerful protective mechanism common to all mankind. The availability of iron is the heart of the matter and the successful functioning of these antibacterial systems depends entirely upon an extremely low level of free ionic iron (10(-18) M) in normal tissue fluids. This in turn depends on well-oxygenated tissues where the oxidation-reduction potential (Eh) and pH control the binding of iron by unsaturated transferrin and lactoferrin. Bacterial virulence is greatly enhanced by freely available iron, such as that in fully-saturated transferrin or free haemoglobin. Following trauma a fall in tissue Eh and pH due to ischaemia, plus the reducing powers of bacteria, can make iron in transferrin freely available and abolish the bactericidal properties of tissue fluids with disastrous results for the host. Hyperbaric oxygen is a possible therapeutic measure that could restore normal bactericidal systems in infected tissues by raising the Eh and pH.
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PMID:Iron and infection: the heart of the matter. 1570 5


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