Using Co-culture and Bioinformatics to Discover New Antibiotic Bioactivities

利用共培养和生物信息学发现新的抗生素生物活性

基本信息

批准号：
10056652
负责人：
Elizabeth Anne Shank
金额：
$ 23.02万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2021-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant) There has been a frightening rise in the incidence of disease-causing bacteria resistant to commonly used antibiotics. We therefore urgently need to identify additional molecules to use as antibiotics. Bacteria themselves have historically been the best source for antibiotics and other related 'secondary metabolites'. While the most common and abundant microbial antibiotics have already been harvested as "low-hanging fruit," microbes remain a deep potential source of new secondary metabolites. A critical barrier to obtaining these compounds, however, has been that bacteria rarely produce their full repertoire of secondary metabolites when cultured in the laboratory. What we lack therefore are efficient mechanisms to stimulate the synthesis of these dormant genes required to synthesize these additional, potentially novel, antibiotics. Bacteria grown in co-culture appear to up-regulate their production of secondary metabolites to act as interspecies signaling cues. Our central hypothesis is that co-culture will stimulate the production of molecules not produced in mono-culture, some of which may be previously uncharacterized antibiotics. We will test this hypothesis using the following approaches. In Aim 1 we will use imaging mass spectrometry to broadly detect the production of compounds produced specifically in co-culture, while in Aim 2 we will take a targeted approach and use bioinformatics to identify bacterial strains encoding proteins predicted to create novel secondary metabolites, and use co-culture to stimulate their production. Finally, in Aim 3 we will test the various co-culture-induced metabolites obtained in the previous two aims for antibiotic activity against human pathogens. The most promising leads will be isolated and chemically identified. Our research proposes to exploit microbial co-culture to elicit the production of bacterial metabolites to identify newly discovered antibiotics. Ultimately, the results from this research will contribute to our long-term goal of ensuring that microbes continue to provide us with the building blocks necessary to replenish our arsenal of antibiotics for therapeutic use.

描述（由申请人提供）引起疾病的细菌的发生率升高，通常将抗生素抗生素抗生素抗生素。 SE代谢的曲目都需要在这些额外的新型抗生素中作为单个文化提示的次要代谢。将质谱质谱法对共同培养的特殊产生的化合物进行质谱，并使用生物信息学识别编码预测的蛋白质的BACTRAIN，这些蛋白质预测了crectel二级代谢物SE的生产。对人类病原体的抗生素活性将被分离出来，并在化学上鉴定出微生物的共同培养物。为我们提供埋葬区块，o补充了我们的抗生素武器以供治疗用途。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Natural-Product Antibiotics: Cues for Modulating Bacterial Biofilm Formation.

DOI：
10.1016/j.tim.2017.06.003
发表时间：
2017-12
期刊：
Trends in microbiology
影响因子：
15.9
作者：
Townsley L;Shank EA
通讯作者：
Shank EA

Cyclic di-AMP Acts as an Extracellular Signal That Impacts Bacillus subtilis Biofilm Formation and Plant Attachment.

DOI：
10.1128/mbio.00341-18
发表时间：
2018-03-27
期刊：
mBio
影响因子：
6.4
作者：
Townsley L;Yannarell SM;Huynh TN;Woodward JJ;Shank EA
通讯作者：
Shank EA

Extensive cellular multi-tasking within Bacillus subtilis biofilms.

DOI：
10.1128/msystems.00891-22
发表时间：
2023-08-31
期刊：
mSystems
影响因子：
6.4
作者：
通讯作者：

Large-Scale Bioinformatics Analysis of Bacillus Genomes Uncovers Conserved Roles of Natural Products in Bacterial Physiology.

DOI：
10.1128/msystems.00040-17
发表时间：
2017-11
期刊：
mSystems
影响因子：
6.4
作者：
Grubbs KJ;Bleich RM;Santa Maria KC;Allen SE;Farag S;AgBiome Team;Shank EA;Bowers AA
通讯作者：
Bowers AA

Rhizobacteria Impact Colonization of Listeria monocytogenes on Arabidopsis thaliana Roots.