Novel mechanisms of DNA repair and cell cycle regulation in bacteria
细菌 DNA 修复和细胞周期调控的新机制
基本信息
- 批准号:9922340
- 负责人:
- 金额:$ 37.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAntibiotic ResistanceAntibiotic TherapyBacillus subtilisBacteriaBacterial Antibiotic ResistanceCell CycleCell Cycle CheckpointCell Cycle ProgressionCell Cycle RegulationCell ProliferationCell Proliferation RegulationCellsDNADNA DamageDNA RepairDNA Repair PathwayDNA Sequence RearrangementDNA damage checkpointDefectDiseaseDisinfectantsEconomic BurdenEnvironmentExcision RepairExposure toGenesGenomeGoalsGram-Positive BacteriaGrowthHealthcare SystemsHospitalsHumanImpairmentLeadListeria monocytogenesMalignant NeoplasmsMedicineMutationNosocomial InfectionsOrganismPathway interactionsProcessProteinsRecoveryResearchSourceStressUnited Statesantimicrobialclinically relevantenvironmental stressorexperimental studygene productgenome integritygenome-widehealth care economicshuman pathogenmethicillin resistant Staphylococcus aureusnovelpathogenpathogenic bacteriarepairedresponse
项目摘要
Project Summary:
A major problem in medicine today is the emergence and persistence of antibiotic resistant bacteria. Although
bacteria have evolved several strategies to grow in harsh environments, many bacterial species broadly cope
in unfavorable conditions by regulating growth and through inducing DNA damage responses. In fact, all
organisms respond to DNA damage by enlisting DNA repair pathways and by regulating cell cycle progression.
Bacterial cells are constantly exposed to a broad spectrum of DNA damage caused by intracellular sources,
environmental stressors, antibiotic treatments, and disinfectants applied in hospital settings. Although DNA
repair and cell cycle checkpoints have been well studied in some bacteria, far less is known about these
processes in Gram-positive bacteria. One major challenge is that even for the most well studied Gram-positive
bacterium, Bacillus subtilis, almost half of the genes in the genome are of unknown function, representing a
critical and fundamental gap in our understanding of how these bacteria mitigate stress that affects growth and
proliferation. While Bacillus subtilis does not cause disease, it is closely related to a number of important
human pathogens, including Methicillin-resistant Staphylococcus aureus, Listeria monocytogenes and several
other pathogens that are responsible for many hospital-acquired infections, which impose significant economic
burdens on our healthcare system annually. Therefore, it is important to understand how a broad group of
clinically relevant bacteria respond to DNA damage and regulate cell proliferation. The long-term goal of this
research is to understand the contribution of unstudied genes and novel mechanisms to DNA repair and cell
cycle regulation in Gram-positive bacteria. We used large-scale genome-wide approaches to identify several
uncharacterized genes that are highly conserved among Gram-positive bacteria and critical for DNA repair and
regulation of cell proliferation. Two of these gene products define a new DNA excision repair pathway while
four other genes are critical for DNA damage checkpoint recovery, allowing cells to re-enter the cell cycle after
the damage has been repaired. We expand these experiments to continue to identify novel interactions with
regulatory partners that control initiation timing and cell proliferation. We expect these studies will result in the
complete mechanistic characterization of proteins involved in initiation, DNA repair, and cell cycle checkpoints.
All of the genes we propose to study are either essential or cause severe growth defects when impaired,
underscoring their importance as possible targets for novel antimicrobial therapies.
项目总结:
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Lyle Simmons其他文献
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{{ truncateString('Lyle Simmons', 18)}}的其他基金
Novel mechanisms of DNA repair and cell cycle regulation in bacteria
细菌 DNA 修复和细胞周期调控的新机制
- 批准号:
10334406 - 财政年份:2019
- 资助金额:
$ 37.31万 - 项目类别:
Novel mechanisms of DNA repair and cell cycle regulation in bacteria
细菌 DNA 修复和细胞周期调控的新机制
- 批准号:
10559506 - 财政年份:2019
- 资助金额:
$ 37.31万 - 项目类别:
Novel mechanisms of DNA repair and cell cycle regulation in bacteria
细菌 DNA 修复和细胞周期调控的新机制
- 批准号:
10090614 - 财政年份:2019
- 资助金额:
$ 37.31万 - 项目类别:
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