Imbalance between cell biomass production and envelope biosynthesis underpins the bactericidal activity of cell wall -targeting antibiotics
细胞生物量产生和包膜生物合成之间的不平衡是细胞壁靶向抗生素杀菌活性的基础
基本信息
- 批准号:2884862
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:英国
- 项目类别:Studentship
- 财政年份:2023
- 资助国家:英国
- 起止时间:2023 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
The majority of our clinically most successful antibiotics target surprisingly few cellular processes. The prominent first-line antibiotic-classes penicillins and cephalosporins, but also the last resort antibiotics vancomycin and daptomycin that are used to treat life-threatening multidrug resistant infections, target the bacterial cell wall synthesis machinery. Despite extensive research, how cell wall -targeting antibiotics kill bacteria and why they are clinically so exceptionally successful has remained enigmatic. The textbook explanation for the bactericidal activity of cell wall -targeting antibiotic is induced cell lysis. However, this ignores the fact that bacteria can die faster than they lyse, and that lysis is frequently not required for efficient killing. Recently, we made the striking discovery that wall-targeting antibiotics trigger a cascade of cellular disturbances that are independent of the induced cell lysis process. Hence, to understand how this prominent class of antibiotics unfolds its antibacterial properties, the cellular processes leading to the lysis-independent killing now needs to be studied in detail. Studying such processes for known antibiotics is important to truly understand how widely used antibiotic classes work, but also to decipher why they share a comparatively low rate of antimicrobial resistance (AMR) development, a property that is key for their clinically success. Crucially, studying these processes will allow us to guide the development of the next generation of new antibiotics towards cellular targets with intrinsically lower risk of resistance development. In this closely collaborative project between the groups of Henrik Strahl (Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University) and Rebecca Corrigan (School of Biosciences, University of Sheffield), the newly discovered mode of action of cell targeting antibiotics will be analysed in the Gram-negative model organism Escherichia coli. The research programme makes extensive use of advanced microscopy techniques such as microfluidic devises, super resolution microscopy and high-speed imaging, combined with bacterial genetics, growth dynamics, and antibiotic resistance and stress profiling.
大多数临床上最成功的抗生素靶向的细胞过程很少。主要的一线抗生素类青霉素和头孢菌素,以及用于治疗危及生命的多重耐药感染的最后手段抗生素万古霉素和达托霉素,靶向细菌细胞壁合成机制。尽管进行了广泛的研究,但靶向细胞壁的抗生素如何杀死细菌,以及它们在临床上如此成功的原因仍然是个谜。教科书上对细胞壁靶向抗生素的杀菌活性的解释是诱导细胞溶解。然而,这忽略了细菌可以比它们裂解更快地死亡的事实,并且裂解通常不是有效杀死所需的。最近,我们取得了惊人的发现,壁靶向抗生素触发级联的细胞干扰是独立的诱导细胞裂解过程。因此,为了了解这类突出的抗生素如何发挥其抗菌特性,现在需要详细研究导致不依赖裂解的杀伤的细胞过程。研究已知抗生素的这些过程对于真正了解广泛使用的抗生素类别如何工作非常重要,而且还可以解释为什么它们具有相对较低的抗菌素耐药性(AMR)发展率,这是其临床成功的关键。至关重要的是,研究这些过程将使我们能够指导下一代新抗生素的开发,使其朝着具有内在较低耐药性发展风险的细胞靶点发展。在Henrik Strahl(纽卡斯尔大学生物科学研究所细菌细胞生物学中心)和Rebecca科里根(谢菲尔德大学生物科学学院)小组之间的这个密切合作项目中,将在革兰氏阴性模式生物大肠杆菌中分析新发现的细胞靶向抗生素的作用模式。该研究计划广泛使用先进的显微镜技术,如微流体装置,超分辨率显微镜和高速成像,结合细菌遗传学,生长动力学,抗生素耐药性和应力分析。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
其他文献
吉治仁志 他: "トランスジェニックマウスによるTIMP-1の線維化促進機序"最新医学. 55. 1781-1787 (2000)
Hitoshi Yoshiji 等:“转基因小鼠中 TIMP-1 的促纤维化机制”现代医学 55. 1781-1787 (2000)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
LiDAR Implementations for Autonomous Vehicle Applications
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
吉治仁志 他: "イラスト医学&サイエンスシリーズ血管の分子医学"羊土社(渋谷正史編). 125 (2000)
Hitoshi Yoshiji 等人:“血管医学与科学系列分子医学图解”Yodosha(涉谷正志编辑)125(2000)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Effect of manidipine hydrochloride,a calcium antagonist,on isoproterenol-induced left ventricular hypertrophy: "Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,K.,Teragaki,M.,Iwao,H.and Yoshikawa,J." Jpn Circ J. 62(1). 47-52 (1998)
钙拮抗剂盐酸马尼地平对异丙肾上腺素引起的左心室肥厚的影响:“Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
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('', 18)}}的其他基金
An implantable biosensor microsystem for real-time measurement of circulating biomarkers
用于实时测量循环生物标志物的植入式生物传感器微系统
- 批准号:
2901954 - 财政年份:2028
- 资助金额:
-- - 项目类别:
Studentship
Exploiting the polysaccharide breakdown capacity of the human gut microbiome to develop environmentally sustainable dishwashing solutions
利用人类肠道微生物群的多糖分解能力来开发环境可持续的洗碗解决方案
- 批准号:
2896097 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
A Robot that Swims Through Granular Materials
可以在颗粒材料中游动的机器人
- 批准号:
2780268 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Likelihood and impact of severe space weather events on the resilience of nuclear power and safeguards monitoring.
严重空间天气事件对核电和保障监督的恢复力的可能性和影响。
- 批准号:
2908918 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Proton, alpha and gamma irradiation assisted stress corrosion cracking: understanding the fuel-stainless steel interface
质子、α 和 γ 辐照辅助应力腐蚀开裂:了解燃料-不锈钢界面
- 批准号:
2908693 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Field Assisted Sintering of Nuclear Fuel Simulants
核燃料模拟物的现场辅助烧结
- 批准号:
2908917 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Assessment of new fatigue capable titanium alloys for aerospace applications
评估用于航空航天应用的新型抗疲劳钛合金
- 批准号:
2879438 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Developing a 3D printed skin model using a Dextran - Collagen hydrogel to analyse the cellular and epigenetic effects of interleukin-17 inhibitors in
使用右旋糖酐-胶原蛋白水凝胶开发 3D 打印皮肤模型,以分析白细胞介素 17 抑制剂的细胞和表观遗传效应
- 批准号:
2890513 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
Understanding the interplay between the gut microbiome, behavior and urbanisation in wild birds
了解野生鸟类肠道微生物组、行为和城市化之间的相互作用
- 批准号:
2876993 - 财政年份:2027
- 资助金额:
-- - 项目类别:
Studentship
相似海外基金
Tools to Control and Monitor Van der Waals Forces between Nanoparticles: Quantitative Insights on Biological, Environmental, and Fungal Cell Interactions.
控制和监测纳米颗粒之间范德华力的工具:对生物、环境和真菌细胞相互作用的定量见解。
- 批准号:
2335597 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Continuing Grant
The molecular basis of T cell receptor cross-reactivity between MHC and MR1
MHC 和 MR1 之间 T 细胞受体交叉反应的分子基础
- 批准号:
DP240102905 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Discovery Projects
CAREER: Predictive Multiscale Modeling of Cell Migration through Pores between Endothelial Cells
职业:通过内皮细胞之间的孔进行细胞迁移的预测多尺度建模
- 批准号:
2339054 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
Cross talk between DNA replication and LPS biosynthesis during cell growth
细胞生长过程中 DNA 复制和 LPS 生物合成之间的串扰
- 批准号:
BB/Y001265/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Research Grant
Elucidation of molecular mechanisms of interaction between colorectal cancer cells and stromal cells in tumor budding area
阐明结直肠癌细胞与肿瘤出芽区基质细胞相互作用的分子机制
- 批准号:
23K15489 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Early-Career Scientists
Analysis of the association between the cell death and inflammation in monogenic autoinflammatory diseases
单基因自身炎症性疾病中细胞死亡与炎症的关联分析
- 批准号:
23K15335 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Early-Career Scientists
The study on the relationship between regulated cell death and prion diseases
调节性细胞死亡与朊病毒病关系的研究
- 批准号:
22KJ0128 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for JSPS Fellows
Novel application of pharmaceutical AMD3100 to reduce risk in opioid use disorder: investigations of a causal relationship between CXCR4 expression and addiction vulnerability
药物 AMD3100 降低阿片类药物使用障碍风险的新应用:CXCR4 表达与成瘾脆弱性之间因果关系的研究
- 批准号:
10678062 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Decoding dynamic interplay between signaling and membranes in chemotaxis bymolecular actuators
通过分子致动器解码趋化中信号传导和膜之间的动态相互作用
- 批准号:
10846921 - 财政年份:2023
- 资助金额:
-- - 项目类别:
The Association Between Aging, Inflammation, and Clinical Outcomes in Acute Respiratory Distress Syndrome
衰老、炎症与急性呼吸窘迫综合征临床结果之间的关联
- 批准号:
10722669 - 财政年份:2023
- 资助金额:
-- - 项目类别: