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presence of oxalobacter formigenes in the intestinal tract is associated with the absence of calcium oxalate urolith formation in dogs.the incidence of calcium oxalate (caox) urolithiasis in dogs has increased steadily over the last two decades. a potential mechanism to minimize caox urolithiasis is to reduce enteric absorption of dietary oxalate by oxalate-metabolizing enteric bacteria. enteric colonization of oxalobacter formigenes, an anaerobe which exclusively relies on oxalate metabolism for energy, is correlated with absence of hyperoxaluria or caox urolithiasis or both in humans and laboratory animals. we thus hypothesiz ...201222223029
intestinal transport of an obdurate anion: oxalate.in this review, we focus on the role of gastrointestinal transport of oxalate primarily from a contemporary physiological standpoint with an emphasis on those aspects that we believe may be most important in efforts to mitigate the untoward effects of oxalate. included in this review is a general discussion of intestinal solute transport as it relates to oxalate, considering cellular and paracellular avenues, the transport mechanisms, and the molecular identities of oxalate transporters. in addi ...200515565438
experimental tests of a homology model for oxlt, the oxalate transporter of oxalobacter formigenes.using the x-ray structure of the glycerol 3-phosphate transporter (glpt), we devised a model for the distantly related oxalate transporter, oxlt. the model accommodates all earlier biochemical information on oxlt, including the idea that lys-355 lies on the permeation pathway, and predicts that lys-355 and a second positive center, arg-272, comprise the binding site for divalent oxalate. study of r272k, r272a, and r272q derivatives verifies that arg-272 is essential, and comparisons with glpt sh ...200515932938
oxalate-degrading providencia rettgeri isolated from human stools.oxalate-degrading bacteria are thought to metabolize intestinal oxalate and thus decrease the urinary excretion of oxalate by reducing its intestinal absorption.200515985073
structural basis for activation of the thiamin diphosphate-dependent enzyme oxalyl-coa decarboxylase by adenosine diphosphate.oxalyl-coenzyme a decarboxylase is a thiamin diphosphate-dependent enzyme that plays an important role in the catabolism of the highly toxic compound oxalate. we have determined the crystal structure of the enzyme from oxalobacter formigenes from a hemihedrally twinned crystal to 1.73 a resolution and characterized the steady-state kinetic behavior of the decarboxylase. the monomer of the tetrameric enzyme consists of three alpha/beta-type domains, commonly seen in this class of enzymes, and the ...200516216870
an animal model of calcium oxalate urolithiasis based on a cyclooxygenase 2 selective inhibitor.our aim was to develop a stone-forming animal model involving renal tubular injury using a cyclooxygenase 2 selective inhibitor. male sprague-dawley rats fed chow containing 3% sodium oxalate with or without 100 mg/kg celecoxib were compared to animals fed normal chow. rats were killed after 2 or 4 weeks and the kidneys were harvested for morphological examination. collections of 24-h urine were made before kidney harvest. after 2 weeks only a few crystals were observed in rats that received oxa ...200516311770
oxalobacter sp. reduces urinary oxalate excretion by promoting enteric oxalate secretion.the primary goal of this study was to test the hypothesis that oxalobacter colonization alters colonic oxalate transport thereby reducing urinary oxalate excretion. in addition, we examined the effects of intraluminal calcium on oxalobacter colonization and tested the hypothesis that endogenously derived colonic oxalate could be degraded by lyophilized oxalobacter enzymes targeted to this segment of the alimentary tract. oxalate fluxes were measured across short-circuited, in vitro preparations ...200616518326
oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1.primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. as treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by oxalobactor formigenes. oxalobacter was orally administered for 4 weeks as frozen paste (ixoc-2) or as enteric-coated capsules (ixoc-3). nine patients (five with normal renal function, one after liver-kidney transplantation, and three with renal failure) completed the ixoc- ...200616850020
analysis of substrate-binding elements in oxlt, the oxalate:formate antiporter of oxalobacter formigenes.an oxlt homology model suggests r272 and k355 in transmembrane helices 8 and 11, respectively, are critical to oxlt-mediated transport. we offer positive evidence supporting this idea by studying oxlt function after cysteine residues were separately introduced at these positions. without further treatment, both mutant proteins had a null phenotype when they were reconstituted into proteoliposomes. by contrast, significant recovery of function occurred when proteoliposomes were treated with mtsea ...200616922510
treatment of the primary hyperoxalurias: a new chapter.despite advances in the enzymology, molecular genetics, and clinical knowledge of the primary hyperoxalurias, few treatments are available. oxalobacter formigenes is a promising new therapy with potential to induce secretion of oxalate into the intestinal lumen, where it can be degraded by the bacteria.200616988727
cloning and identification of frc gene from oxalobacter frmigenes.the cloning and identification of frc gene from oxalobacter formigenes in the intestines of chinese people were conducted. the genomic dna of oxalobacter formigenes was extracted. frc gene fragment was amplified by polymerase chain reaction (pcr) and linked with pegfp-c1. the recombinant plasmid was designated pegfp-frc and was identified by restriction-enzyme digestion and sequencing. human embryo kidney 293 cells were transfected with pegfp-frc, then rt-pcr and western blotting were performed ...200717497294
enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization with oxalobacter.oxalobacter colonization of rat intestine was previously shown to promote enteric oxalate secretion and elimination, leading to significant reductions in urinary oxalate excretion (hatch et al. kidney int 69: 691-698, 2006). the main goal of the present study, using a mouse model of primary hyperoxaluria type 1 (ph1), was to test the hypothesis that colonization of the mouse gut by oxalobacter formigenes could enhance enteric oxalate secretion and effectively reduce the hyperoxaluria associated ...201021163900
oxalobacter colonization in the morbidly obese and correlation with urinary stone risk.objectives: to establish the baseline preoperative prevalence of oxalobacter formigenes (of) colonization in a cohort of obese patients scheduled for roux-en-y gastric bypass (rygb) and determine the effect of of colonization on urinary oxalate excretion. it has been proposed that loss of of colonization after rygb may contribute to the development of hyperoxaluria. methods: adult patients scheduled to undergo rygb were requested to provide a stool specimen and 24-hour urine collection before su ...201121529902
Oligomeric state of the oxalate transporter, OxlT.OxlT, the oxalate transporter of Oxalobacter formigenes, was studied to determine its oligomeric state in solution and in the membrane. Three independent approaches were used. First, we used triple-detector (SEC-LS) size exclusion chromatography to analyze purified OxlT in detergent/lipid micelles. These measurements evaluate protein mass in a manner independent of contributions from detergent and lipid; such work shows an average OxlT mass near 47 kDa for detergent-solubilized material, consist ...201121866906
the construction of an oxalate-degrading intestinal stem cell population in mice: a potential new treatment option for patients with calcium oxalate calculus.about 80% of all urological stones are calcium oxalate, mainly caused by idiopathic hyperoxaluria (ih). the increased absorption of oxalate from the intestine is the major factor underlying ih. the continuous self-renewal of the intestinal epithelium is due to the vigorous proliferation and differentiation of intestinal stem cells. if the intestinal stem cell population can acquire the ability to metabolize calcium oxalate by means of oxc and frc transgenes, this will prove a promising new thera ...201121892601
quantitative analysis of colonization with real-time pcr to identify the role of oxalobacter formigenes in calcium oxalate urolithiasis.the objective of the study was to quantitatively measure the number of oxalobacter formigenes (o. formigenes) colonizations in the gastrointestinal tract in calcium oxalate-forming patients with real-time polymerase chain reaction (pcr). calcium oxalate-forming patients (n: 27) were included in the study. serum calcium, sodium, potassium, urea and creatinine levels, as well as 24 h urine levels of calcium and oxalate were measured. the numbers of o. formigenes colonies in stool samples were dete ...201222215293
determination of oxalyl-coenzyme a decarboxylase activity in oxalobacter formigenes and lactobacillus acidophilus by capillary electrophoresis.oxalyl-coenzyme a decarboxylase (oxc) is a key enzyme in the catabolism of the highly toxic oxalate, catalysing the decarboxylation of oxalyl-coenzyme a (ox-coa) to formyl-coenzyme a (for-coa). in the present study, a capillary electrophoretic (ce) method was proposed for the assessment of the activity of recombinant oxc from two bacteria, namely oxalobacter formigenes dsm 4420 and lactobacillus acidophilus la 14. in particular, the degradation of the substrate ox-coa occurring in the enzymatic ...200717499563
stable expression of the oxc and frc genes from oxalobacter formigenes in human embryo kidney 293 cells: implications for gene therapy of hyperoxaluria.hyperoxaluria can lead to multiple pathologic conditions such as recurrent urolithiasis, oxalosis, nephrocalcinosis and even renal failure, but there is no known oxalate-degrading pathway in the human body, and current therapeutic options for patients with hyperoxaluria are limited. oxalyl-coa decarboxylase and formyl-coa transferase are the key enzymes in the oxalate catabolism of oxalobacter formigenes which dwell in the intestine of vertebrates and have an important symbiotic relationship wit ...200717786282
reinvestigation of the catalytic mechanism of formyl-coa transferase, a class iii coa-transferase.formyl-coenzyme a transferase from oxalobacter formigenes belongs to the class iii coenzyme a transferase family and catalyzes the reversible transfer of a coa carrier between formyl-coa and oxalate, forming oxalyl-coa and formate. formyl-coa transferase has a unique three-dimensional fold composed of two interlaced subunits locked together like rings of a chain. we here present an intermediate in the reaction, formyl-coa transferase containing the covalent beta-aspartyl-coa thioester, adopting ...200818162462
oxalobacter formigenes may reduce the risk of calcium oxalate kidney stones.most kidney stones are composed primarily of calcium oxalate. oxalobacter formigenes is a gram-negative, anaerobic bacterium that metabolizes oxalate in the intestinal tract and is present in a large proportion of the normal adult population. it was hypothesized that the absence of o. formigenes could lead to increased colonic absorption of oxalate, and the subsequent increase in urinary oxalate could favor the development of stones. to test this hypothesis, a case-control study involving 247 ad ...200818322162
cysteine scanning mutagenesis of tm5 reveals conformational changes in oxlt, the oxalate transporter of oxalobacter formigenes.we constructed a single-cysteine panel encompassing tm5 of the oxalate transporter, oxlt. the 25 positions encompassed by tm5 were largely tolerant of mutagenesis, and functional product was recovered for 21 of the derived variants. for these derivatives, thiol-directed mts-linked agents (mtsea, mtsce, and mtses) were used as probes of transporter function, yielding 11 mutants that responded to probe treatment, as indicated by effects on oxalate transport. further study identified three biochemi ...200818452311
a critical analysis of the role of gut oxalobacter formigenes in oxalate stone disease.hyperoxaluria is a major risk factor for the formation of calcium oxalate stones, but dietary restriction of oxalate intake might not be a reliable approach to prevent recurrence of stones. hence, other approaches to reduce urinary oxalate to manage stone disease have been explored. the gut-dwelling obligate anaerobe oxalobacter formigenes (of) has attracted attention for its oxalate-degrading property. in this review we critically evaluate published studies and identify major gaps in knowledge. ...200919021605
recent advances in the pathophysiology of nephrolithiasis.over the past 10 years, major progress has been made in the pathogenesis of uric acid and calcium stones. these advances have led to our further understanding of a pathogenetic link between uric acid nephrolithiasis and the metabolic syndrome, the role of oxalobacter formigenes in calcium oxalate stone formation, oxalate transport in slc26a6-null mice, the potential pathogenetic role of randall's plaque as a precursor for calcium oxalate nephrolithiasis, and the role of renal tubular crystal ret ...200919078968
presence of oxalobacter formigenes in the stool of healthy dogs. 200919193501
probiotic-induced reduction of gastrointestinal oxalate absorption in healthy subjects.both a high dietary oxalate intake and increased intestinal absorption appear to be major causes of elevated urine oxalate, a risk factor for kidney stone formation. by favorably altering the gastrointestinal bacterial population, probiotics have the potential to lower oxalate absorption/urinary excretion. this study assessed whether a 4-wk daily consumption of a commercially available probiotic by 11 healthy volunteers (8 females, 3 males), aged 21-36 y, would decrease oxalate absorption. the s ...201020224931
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