Inhibiting hydrogen-dependent pathogen growth via nickel chelation
Inhibiting hydrogen-dependent pathogen growth via nickel chelation
批准号:
9293975
负责人:
ROBERT J. MAIER
金额:
$22.5万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-06-10 至 2019-05-31
关键词:
AffectAffinityAnimal ExperimentsAnimalsAreaAttenuatedBacteriaBindingBinding ProteinsBiologicalBiological AssayCampylobacterChelating AgentsChemicalsCysteineDataDevelopmentDiseaseEffectivenessEncapsulatedEnterobacteriaceaeEnzymesFDA approvedGleanGlycolatesGoalsGrowthHistidineHumanHydrogenHydrogenaseIndividualMedicineMetalsMicellesMolecularMusNanosphereNatureNickelPeptidesPersonsPolymersProteinsSalmonellaSalmonella entericaSalmonella infectionsSeriesShigellaSmall IntestinesSpecificityStomachStructureSystemTestingToxic effectTyphoid FeverUreaseVirulenceWorkattenuationbasebiodegradable polymerchelationcombatdeprivationdesignenteric pathogenenterotoxigenic Escherichia coliimprovedin vivometal chelatormicrobiotamolecular hydrogenmutantnanoparticlenovel strategiespathogenpreventprotein complexscale up
中文摘要
总结
英文摘要
Summary
Salmonella and other pathogens use host microbiota-produced molecular hydrogen (H2) to
grow within the host; they do so via conserved nickel-containing hydrogenase enzymes. A
new exploratory approach is proposed to assess the ability of natural histidine- and
cysteine-containing metal-binding peptides to combat salmonellosis. The rationale is based
on the effectiveness of nickel chelating chemicals to attenuate Salmonella hydrogenase
expression and even salmonellosis in mice. However, the known chelators are toxic to the
animal. Instead, small peptides that have inherently high capacity for nickel binding will be
assessed first for their ability to inhibit H2 dependent growth of the pathogen in the lab and
then within the animal. The degree of inhibition of H2-dependent growth by nickel
deprivation will be assigned to individual hydrogen-utilizing hydrogenases by studying
mutant strains. The molecular nature of the chelator, including use of Ni-binding domain
fusions, as well as the nanoparticle host delivery regimes will be studied to fully assess the
salmonella-inhibitory affects. Testing of truncated and fused versions composed of identified
Ni-sequestering domains is expected to improve chelator (nickel-binding) effectiveness per
mg of peptide, while encapsulating them in biodegradable polymeric micelles is expected to
promote their gastric survival so their effectiveness in vivo can be assessed in an
exploratory way. For in vivo testing, peptide-based chelation in the small intestine where
Salmonella growth is rapid and dependent on H2 via an identified Ni-hydrogenase is
desired. The work is expected to apply to growth attenuation of nickel-requiring enteric
pathogens, including Salmonella, Shigella, enterotoxigenic E. coli, and Campylobacter, but
the new metal chelator development may apply to many areas of medicine.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
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批准号:8132560
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项目类别:
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资助金额:$22.05万
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财政年份:2010
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负责人:ROBERT J. MAIER
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依托单位:
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批准号:7737703
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项目类别:
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资助金额:$18.56万
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财政年份:2010
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负责人:ROBERT J. MAIER
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依托单位:
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批准号:7849924
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项目类别:
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资助金额:$22.28万
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财政年份:2009
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负责人:ROBERT J. MAIER
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依托单位:
Amino Acid Repair Activity in Helicobacter pylori
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批准号:8197120
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资助金额:$36.14万
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财政年份:2008
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负责人:ROBERT J. MAIER
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依托单位:
Amino Acid Repair Activity in Helicobacter pylori
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批准号:7994871
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项目类别:
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资助金额:$36.14万
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财政年份:2008
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负责人:ROBERT J. MAIER
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依托单位:
Amino Acid Repair Activity in Helicobacter pylori
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批准号:7580477
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项目类别:
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资助金额:$36.26万
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财政年份:2008
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负责人:ROBERT J. MAIER
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依托单位:
Amino Acid Repair Activity in Helicobacter pylori
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批准号:7742166
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项目类别:
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资助金额:$36.51万
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财政年份:2008
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负责人:ROBERT J. MAIER
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依托单位:
Repair of methionine residues in H. pylori catalase
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批准号:7530074
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项目类别:
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资助金额:$7.38万
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财政年份:2008
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负责人:ROBERT J. MAIER
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依托单位:
Amino Acid Repair Activity in Helicobacter pylori
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批准号:8389666
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项目类别:
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资助金额:$33.97万
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财政年份:2008
-
负责人:ROBERT J. MAIER
-
依托单位:
Nickel Metabolism in Helicobacter pylori
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批准号:6872172
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项目类别:
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资助金额:$25.76万
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财政年份:2004
-
负责人:ROBERT J. MAIER
-
依托单位:
Nickel Metabolism in Helicobacter pylori
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批准号:7026396
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项目类别:
-
资助金额:$25.15万
-
财政年份:2004
-
负责人:ROBERT J. MAIER
-
依托单位:
Nickel Metabolism in Helicobacter pylori
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批准号:6771531
-
项目类别:
-
资助金额:$25.43万
-
财政年份:2004
-
负责人:ROBERT J. MAIER
-
依托单位:
Virulence Determinants in Helicobacter hepaticus
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批准号:6769898
-
项目类别:
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资助金额:$7.36万
-
财政年份:2003
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负责人:ROBERT J. MAIER
-
依托单位:
Virulence Determinants in Helicobacter hepaticus
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批准号:6686265
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项目类别:
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资助金额:$7.36万
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财政年份:2003
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负责人:ROBERT J. MAIER
-
依托单位:
Oxidative Stress and Survival of Helicobacter pylori
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批准号:6365043
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项目类别:
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资助金额:$18.1万
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财政年份:2001
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负责人:ROBERT J. MAIER
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依托单位:
Oxidative Stress and Survival of Helicobacter pylori
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批准号:6761795
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项目类别:
-
资助金额:$18.1万
-
财政年份:2001
-
负责人:ROBERT J. MAIER
-
依托单位:
Oxidative Stress and Survival of Helicobacter pylori
-
批准号:6524409
-
项目类别:
-
资助金额:$18.1万
-
财政年份:2001
-
负责人:ROBERT J. MAIER
-
依托单位:
Oxidative Stress and Survival of Helicobacter pylori
-
批准号:6637169
-
项目类别:
-
资助金额:$18.1万
-
财政年份:2001
-
负责人:ROBERT J. MAIER
-
依托单位:
Oxidative Stress and Survival of Helicobacter pylori
-
批准号:6894029
-
项目类别:
-
资助金额:$18.1万
-
财政年份:2001
-
负责人:ROBERT J. MAIER
-
依托单位:
Oxidative Stress and Survival of Helicobacter pylori
-
批准号:6941809
-
项目类别:
-
资助金额:$3.68万
-
财政年份:2001
-
负责人:ROBERT J. MAIER
-
依托单位:
海外基金