D-serine/DsdCXA control of E. coli uropathogenesis
D-丝氨酸/DsdCXA 控制大肠杆菌尿路病变
基本信息
- 批准号:8448312
- 负责人:
- 金额:$ 29.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-06-01 至 2014-01-31
- 项目状态:已结题
- 来源:
- 关键词:AffectBacteriaBladderCarbonCatabolismChemotaxisClinicalCytotoxinD-Serine dehydrataseDevelopmentDipeptidesDrug TargetingEscherichia coliGene ClusterGene ExpressionGene Expression RegulationGenesGeneticGenetic TranscriptionGrantGrowthHemolysinHomologous GeneIn VitroIslandKidneyLaboratoriesLacZ GenesLinkMediatingModelingMusMutationNitrogenPeptidoglycanPhasePhenotypeProteinsRegulationRegulonRoleSepsisSerineSignal TransductionSiteSourceSystemTestingTimeUp-RegulationUrinary tractUrinary tract infectionUropathogenic E. coliVirulenceWorkantimicrobialcell motilitycommunity-acquired UTIfimbriafitnesshuman diseasein vivomutantnosocomial UTInovelnovel vaccinesprotein expressionrecombinasesecretory proteintype 1 fimbriaeuptake
项目摘要
Escherichia coli is the most common cause of community-acquired urinary tract infection
(UTI) and a leading cause of nosocomial UTIs and sepsis. We have focused on a genetic
island at argW in E.coli urosepsis strain CFT073 which contains the dsdCXA genes for D-
serine utilization and ipuAB, homologs of fimBE, the type 1 fimbriae phase-switch
recombinases. A CFT073 dsdA mutant lacking D-serine deaminase is 300-fold more
competitive than wild type CFT073 in colonizing the bladder or kidney of experimentally
infected mice. Compared to CFT073, 44 and 41 genes were respectively up- and down-
regulated in the CFT073 dsdA mutant during murine UTI. Up-regulated genes encoded P
and F1C fimbriae, hemolysin, OmpF, a dipeptide transporter DppA, and several genes with
unknown functions. CFT073 as well as other uropathogenic E. coli show (+) chemotaxis
toward D-serine, but not L-serine as is the case E. coli K-12. ipuA has fimB-like ON-to-OFF
and OFF-to-ON fimS switching activity during murine UTI. A CFT073 dsdA::lacZ
transcriptional fusion undergoes reversible phase-switching albeit by an unidentified
mechanism affected by ipuA and ipuB mutations. ipuA and ipuB also control a fimS-
independent reversible phase switch of a set of genes encoding secreted products that
includes the hemolysin. Therefore, we generated strong support of our original hypotheses
that D-serine represents an important signal for regulation of CFT073 virulence genes and
growth in the urinary tract and that the dsdCXA-linked recombinases mediate phase-state
regulation of important urovirulence and fitness factors besides the type 1 fimbriae. We will
investigate the mechanism whereby elevated intracellular D-serine leads to up-regulation of
urovirulence and fitness genes and characterize loci aside from fimS that are controlled by
the recombinases. We will use the CFT073 dsdA mutant as a model of the DsdA OFF state
to study the roles of P fimbriae and hemolysin in colonization of the murine bladder and
kidney. The objective of our project is to identify and characterize virulence genes for E. coli
involved in serious human diseases. This work will aid development of new vaccines and
antimicrobials. To that end, we have recently acquired evidence that the D-serine
deaminase can serve as a novel drug target for identification of new antimicrobials.
大肠杆菌是社区获得性尿路感染的最常见原因
项目成果
期刊论文数量(69)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The HpmA hemolysin is more common than HlyA among Proteus isolates.
在变形杆菌分离株中,HpmA 溶血素比 HlyA 更常见。
- DOI:10.1128/iai.58.6.1853-1860.1990
- 发表时间:1990
- 期刊:
- 影响因子:3.1
- 作者:Swihart,KG;Welch,RA
- 通讯作者:Welch,RA
Physical characterization of Bacteroides fragilis R plasmid pBF4.
脆弱拟杆菌 R 质粒 pBF4 的物理表征。
- DOI:10.1128/jb.145.2.867-872.1981
- 发表时间:1981
- 期刊:
- 影响因子:3.2
- 作者:Welch,RA;Macrina,FL
- 通讯作者:Macrina,FL
IraL is an RssB anti-adaptor that stabilizes RpoS during logarithmic phase growth in Escherichia coli and Shigella.
- DOI:10.1128/mbio.01043-14
- 发表时间:2014-05-27
- 期刊:
- 影响因子:6.4
- 作者:Hryckowian AJ;Battesti A;Lemke JJ;Meyer ZC;Welch RA
- 通讯作者:Welch RA
Assays of hemolytic toxins.
- DOI:10.1016/0076-6879(94)35179-1
- 发表时间:1994
- 期刊:
- 影响因子:0
- 作者:G. Rowe;Rodney A. Welch
- 通讯作者:G. Rowe;Rodney A. Welch
Non-plasmid associated transfer of antibiotic resistance in Bacteroides.
拟杆菌中抗生素耐药性的非质粒相关转移。
- DOI:10.1093/jac/8.suppl_d.77
- 发表时间:1981
- 期刊:
- 影响因子:0
- 作者:Macrina,FL;Mays,TK;Smith,CJ;Welch,RA
- 通讯作者:Welch,RA
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Rodney A. Welch其他文献
Transferable lincosamide-macrolide resistance in Bacteroides.
拟杆菌中可转移的林可酰胺-大环内酯耐药性。
- DOI:
- 发表时间:
1979 - 期刊:
- 影响因子:2.6
- 作者:
Rodney A. Welch;Kevin R. Jones;F. Macrina - 通讯作者:
F. Macrina
1088 <em>ESCHERICHIA COLI</em> STRAINS FROM CHRONIC PROSTATITIS PATIENTS INVADE PROSTATE EPITHELIAL CELLS AND INDUCE SECRETION OF INFLAMMATORY MEDIATORS
- DOI:
10.1016/j.juro.2012.02.1195 - 发表时间:
2012-04-01 - 期刊:
- 影响因子:0
- 作者:
Li-Lin Cheng;Laura E. Goeser;Alexandra E. Burleigh;Justin J. Lemke;Rodney A. Welch;Walter J. Hopkins - 通讯作者:
Walter J. Hopkins
Rodney A. Welch的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Rodney A. Welch', 18)}}的其他基金
D-serine/DsdCXA control of E. coli uropathogenesis
D-丝氨酸/DsdCXA 控制大肠杆菌尿路病变
- 批准号:
7577111 - 财政年份:2009
- 资助金额:
$ 29.91万 - 项目类别:
D-serine/DsdCXA control of E. coli uropathogenesis
D-丝氨酸/DsdCXA 控制大肠杆菌尿路病变
- 批准号:
8242649 - 财政年份:2009
- 资助金额:
$ 29.91万 - 项目类别:
D-serine/DsdCXA control of E. coli uropathogenesis
D-丝氨酸/DsdCXA 控制大肠杆菌尿路病变
- 批准号:
7885633 - 财政年份:2009
- 资助金额:
$ 29.91万 - 项目类别:
D-serine/DsdCXA control of E. coli uropathogenesis
D-丝氨酸/DsdCXA 控制大肠杆菌尿路病变
- 批准号:
8063183 - 财政年份:2009
- 资助金额:
$ 29.91万 - 项目类别:
D-serine/DsdCXA Control of E coli Uropathogenesis
D-丝氨酸/DsdCXA 控制大肠杆菌尿路病理发生
- 批准号:
7558446 - 财政年份:2008
- 资助金额:
$ 29.91万 - 项目类别:
D-Amino acid and tellurite resistance in NIAID Category A bacterial pathogens
NIAID A 类细菌病原体中的 D-氨基酸和亚碲酸盐耐药性
- 批准号:
7495611 - 财政年份:2007
- 资助金额:
$ 29.91万 - 项目类别:
D-Amino acid and tellurite resistance in NIAID Category A bacterial pathogens
NIAID A 类细菌病原体中的 D-氨基酸和亚碲酸盐耐药性
- 批准号:
7286614 - 财政年份:2007
- 资助金额:
$ 29.91万 - 项目类别:
StcE, an E.coli O157:H7 Protease Specific for C1-Inh
StcE,一种针对 C1-Inh 的大肠杆菌 O157:H7 蛋白酶
- 批准号:
6697423 - 财政年份:2003
- 资助金额:
$ 29.91万 - 项目类别:
StcE, an E.coli O157:H7 Protease Specific for C1-Inh
StcE,一种针对 C1-Inh 的大肠杆菌 O157:H7 蛋白酶
- 批准号:
7162077 - 财政年份:2003
- 资助金额:
$ 29.91万 - 项目类别:
StcE, an E.coli O157:H7 Protease Specific for C1-Inh
StcE,一种针对 C1-Inh 的大肠杆菌 O157:H7 蛋白酶
- 批准号:
7009264 - 财政年份:2003
- 资助金额:
$ 29.91万 - 项目类别:
相似国自然基金
Segmented Filamentous Bacteria激活宿主免疫系统抑制其拮抗菌 Enterobacteriaceae维持菌群平衡及其机制研究
- 批准号:81971557
- 批准年份:2019
- 资助金额:65.0 万元
- 项目类别:面上项目
电缆细菌(Cable bacteria)对水体沉积物有机污染的响应与调控机制
- 批准号:51678163
- 批准年份:2016
- 资助金额:64.0 万元
- 项目类别:面上项目
相似海外基金
Did light dictate ancient diversification of phylogeny and cell structure in the domain bacteria?
光是否决定了细菌领域的古代系统发育和细胞结构的多样化?
- 批准号:
24H00582 - 财政年份:2024
- 资助金额:
$ 29.91万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Cell Wall Formation in Rod Shaped Bacteria
杆状细菌细胞壁的形成
- 批准号:
BB/Y003187/1 - 财政年份:2024
- 资助金额:
$ 29.91万 - 项目类别:
Research Grant
DNA replication dynamics in living bacteria
活细菌中的 DNA 复制动态
- 批准号:
23K25843 - 财政年份:2024
- 资助金额:
$ 29.91万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Conference: Symposium on the Immune System of Bacteria
会议:细菌免疫系统研讨会
- 批准号:
2349218 - 财政年份:2024
- 资助金额:
$ 29.91万 - 项目类别:
Standard Grant
DYNBIOTICS - Understanding the dynamics of antibiotics transport in individual bacteria
DYNBIOTICS - 了解抗生素在单个细菌中转运的动态
- 批准号:
EP/Y023528/1 - 财政年份:2024
- 资助金额:
$ 29.91万 - 项目类别:
Research Grant
NPBactID - Differential binding of peptoid functionalized nanoparticles to bacteria for identifying specific strains
NPBactID - 类肽功能化纳米粒子与细菌的差异结合,用于识别特定菌株
- 批准号:
EP/Y029542/1 - 财政年份:2024
- 资助金额:
$ 29.91万 - 项目类别:
Fellowship
Assembly of the matrix that supports bacteria living in biofilms
支持生活在生物膜中的细菌的基质的组装
- 批准号:
2468773 - 财政年份:2024
- 资助金额:
$ 29.91万 - 项目类别:
Studentship
Manipulating two-component systems to activate cryptic antibiotic pathways in filamentous actinomycete bacteria
操纵双组分系统激活丝状放线菌中的神秘抗生素途径
- 批准号:
BB/Y005724/1 - 财政年份:2024
- 资助金额:
$ 29.91万 - 项目类别:
Research Grant
Engineering Streptomyces bacteria for the sustainable manufacture of antibiotics
工程化链霉菌用于抗生素的可持续生产
- 批准号:
BB/Y007611/1 - 财政年份:2024
- 资助金额:
$ 29.91万 - 项目类别:
Research Grant
CAREER: Interfacial behavior of motile bacteria at structured liquid crystal interfaces
职业:运动细菌在结构化液晶界面的界面行为
- 批准号:
2338880 - 财政年份:2024
- 资助金额:
$ 29.91万 - 项目类别:
Continuing Grant