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Modeling Pheromone Induced Plasmid and Drug Resistance Transfer

信息素诱导质粒和耐药性转移建模

基本信息

批准号：
8824943
负责人：
WEI-SHOU HU
金额：
$ 33.87万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-16 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8824943
关键词：
Accounting Antibiotic Resistance Antibiotics Bacteria Bacterial Antibiotic Resistance Cells Chromosomes Code Complex DNA-Directed RNA Polymerase Drug resistance Enterococcus Enterococcus faecalis Equilibrium Face Family Generations Genes Genetic Transcription Goals Heterogeneity Human Infection Intervention Intestines Investigation Mediating Metabolic Microbe Modeling Nosocomial Infections Operon Partner in relationship Peptide Signal Sequences Peptides Pheromone Plasmids Play Population Population Heterogeneity Process RNA Regulation Repressor Proteins Research Resistance Resources Role Signal Transduction Signaling Molecule Staphylococcus aureus System Systems Analysis Testing Therapeutic Titrations Transcript Virulent Work base cell type fighting inhibitor/antagonist mathematical model peptide pheromone cCF10 promoter quorum sensing resistance gene response transmission process

项目摘要

DESCRIPTION (provided by applicant): Project Summary Enterococcus faecalis is a bacterium found in the intestine of humans as well as in a wide variety of ecological niches. While it is not as virulent as Staphylococcus aureus, it resistance to antibiotics and the ease of its spread among its population has long made E. faecalis a serious therapeutic problem. Our proposed research will examine the mechanism employed for the spread of antibiotic resistance in E. faecalis. The antibiotic resistance gene resides in a plasmid. Different plasmids in the same family carry resistance to different antibiotics. However, each cell does not carry every plasmid, as doing so would increase the metabolic load beyond the point of efficiency. Therefore, each type of plasmid must be spread between cells as necessary. The antibiotic resistant plasmid is spread through a direct cell-cell contact process called conjugation, a process in which the donor cells pass the plasmid with the antibiotic resistance gene to recipient cells. The plasmid carried by donor cells encodes the genes for conjugative transfer of the plasmid as well as for a signal peptide. Upon receipt of the plasmid, the recipient cells then become donor cells. The signal peptide produced by the recipient has long been considered a "mate" sensing molecule for donors to sense the concentration of recipients. Results from our current work using plasmid pCF10 led us to propose that the plasmid encoded signal is a "self" (or quorum) sensing molecule for donor to sense its own concentration. We hypothesize that through the interplay of the two signaling molecules, the donor and recipient cells alter their conjugative dynamics to maintain their plasmid-present antibiotic resistant subpopulation and plasmid- free, faster growing recipient subpopulation. We further hypothesize that a heterogeneous response to the "mate" signal by donor cells in a population provides a competitive advantage; to preserve resources, some donor cells respond earlier and at a low concentration of signaling molecules while others respond later and at a higher concentration of signaling molecules. The titration of the cellular response is mediated by two operons in the plasmid. In our current work we have unveiled a noble mechanism which cells employ to respond to the two signaling molecules. In this proposed research we will develop mathematical models to explore the donor-recipient dynamics. A better understanding of the mechanism of plasmid transfer will help us identify a new way to fight conjugative antibiotic resistance transfer.

描述（由申请人提供）：

项目成果

期刊论文数量（25）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Stromal-derived factor-1 alpha-loaded PLGA microspheres for stem cell recruitment.

DOI：
10.1007/s11095-011-0474-x
发表时间：
2011-10
期刊：
PHARMACEUTICAL RESEARCH
影响因子：
3.7
作者：
Cross, Daisy P.;Wang, Chun
通讯作者：
Wang, Chun

On speeding up stochastic simulations by parallelization of random number generation.

通过随机数生成的并行化来加速随机模拟。

DOI：
10.1016/j.ces.2015.06.066
发表时间：
2015
期刊：
Chemical engineering science
影响因子：
4.7
作者：
Shu,Che-Chi;Tran,Vu;Binagia,Jeremy;Ramkrishna,Doraiswami
通讯作者：
Ramkrishna,Doraiswami

The road to regenerative liver therapies: the triumphs, trials and tribulations.

再生肝疗法的道路：胜利，试验和磨难。

DOI：
10.1016/j.biotechadv.2013.08.022
发表时间：
2013-11-15
期刊：
BIOTECHNOLOGY ADVANCES
影响因子：
16
作者：
Raju, Ravali;Chau, David;Verfaillie, Catherine M.;Hu, Wei-Shou
通讯作者：
Hu, Wei-Shou

Universal labeling of 5'-triphosphate RNAs by artificial RNA ligase enzyme with broad substrate specificity.

DOI：
10.1039/c3cc44454f
发表时间：
2013-08-25
期刊：
Chemical communications (Cambridge, England)
影响因子：
0
作者：
Haugner JC 3rd;Seelig B
通讯作者：
Seelig B

Impact of TiO2 nanoparticles on growth, biofilm formation, and flavin secretion in Shewanella oneidensis.

DOI：
10.1021/ac400486u
发表时间：
2013-06-18
期刊：
ANALYTICAL CHEMISTRY
影响因子：
7.4
作者：
Maurer-Jones, Melissa A.;Gunsolus, Ian L.;Meyer, Ben M.;Christenson, Cole J.;Haynes, Christy L.
通讯作者：
Haynes, Christy L.