How is V. cholerae lifestyle switching controlled?

如何控制霍乱弧菌生活方式的改变？

• 批准号: BB/N005961/1
• 负责人: David Grainger
• 金额: $ 45.02万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN005961%2F1
• 关键词: How; V.; cholerae; lifestyle; switching

Vibrio cholerae is a bacterium. It is the biological agent that causes Cholera, a severe form of diarrhoea. Worldwide, approximately 4 million people are infected by V. cholerae every year. This results in hundreds of thousands of fatalities. Many cases are attributable to an ongoing global pandemic, the 7th to sweep our planet in recorded history. However, disease is also associated with local epidemics; the upsurge of Cholera cases in Haiti, following the 2010 earthquake, being of note. The annual financial cost associated with V. cholerae infections exceeds $3 billion annually. Hence, there is significant commercial interest in solving the "Cholera problem". At present, epidemics may be controlled by vaccinating the population in affected areas. However, currently available Cholera vaccines are poorly effective. Consequently, industrial operations worldwide are identifying strategies to develop better vaccines. The growing problem of resistance to antimicrobial agents is also fueling this trend. The ability of V. cholerae to persist in the environment, and cause disease, is dependent on exploitation of two different environmental niches. Principally, V. cholerae is an aquatic organism that colonises the surface of crustaceans. In this situation, the bacterium's primary source of nutrition is chitin; a component of the shellfish exoskeleton. Thus, V. cholerae forms biofilms on such surfaces. Conversely, when V. cholerae is ingested by fish, or humans, the bacterium's lifestyle is "reprogrammed" so that it can colonise the host. This is beneficial to the bacterium since it can multiply rapidly in hosts before being shed back into the environment. In humans this process is associated with the disease known as Cholera. Understanding how V. cholerae adapts to its different environments is therefore of great interest.In recent work we have shown how applying the next generation of experimental tools can rapidly progress our understanding of bacterial pathogens. We propose to apply such tools to understand lifestyle switching in V. cholerae. Ultimately, by picking apart the control of lifestyle switching, and redesigning V. cholerae to regulate this process differently, we hope to stimulate a new era of vaccine design. We expect that this approach will be applicable to many diseases caused by bacteria. We have identified UK based biopharma likely to benefit from these advances and will liaise closely with them throughout the project. The purpose of this interaction is to maximise the impact of our work and to exploit opportunities that arise for commercialisation. In summary, we will study a globally important pathogen and develop strategies applicable to the control of all bacteria. Importantly, this application comes at a time when alternatives to antibiotics are being sought and the window of opportunity to act is open. We have already fostered links with important "end-users" of our data to maximise the economic impact of our work.

霍乱弧菌是一种细菌。它是引起霍乱的生物制剂，霍乱是一种严重的腹泻形式。全世界每年约有400万人感染霍乱弧菌。这导致数十万人死亡。许多病例可归因于正在进行的全球大流行病，这是有史以来第七次席卷我们的星球。然而，疾病也与地方流行病有关;值得注意的是，2010年地震后海地霍乱病例激增。与霍乱弧菌感染相关的年度财务成本每年超过30亿美元。因此，解决“霍乱问题”具有重大的商业利益。目前，可以通过对受影响地区的人口接种疫苗来控制流行病。然而，目前可用的霍乱疫苗效果不佳。因此，全世界的工业界正在确定开发更好疫苗的战略。日益严重的抗微生物药物耐药性问题也助长了这一趋势。霍乱弧菌在环境中持续存在并引起疾病的能力取决于对两种不同环境生态位的利用。主要地，霍乱弧菌是一种水生生物，定居在甲壳类动物的表面。在这种情况下，细菌的主要营养来源是甲壳素，甲壳素是贝类外骨骼的一种成分。因此，霍乱弧菌在这些表面上形成生物膜。相反，当鱼类或人类摄入霍乱弧菌时，细菌的生活方式被“重新编程”，以便它可以在宿主中定居。这对细菌是有益的，因为它可以在宿主中迅速繁殖，然后再被释放回环境中。在人类中，这一过程与称为霍乱的疾病有关。因此，了解霍乱弧菌如何适应不同的环境是非常有趣的。在最近的工作中，我们已经展示了如何应用下一代实验工具可以快速推进我们对细菌病原体的理解。我们建议应用这些工具来了解霍乱弧菌的生活方式转换。最终，通过分离生活方式转换的控制，并重新设计霍乱弧菌以不同的方式调节这一过程，我们希望刺激疫苗设计的新时代。我们希望这种方法将适用于许多由细菌引起的疾病。我们已经确定了可能从这些进步中受益的英国生物制药公司，并将在整个项目过程中与他们密切联系。这种互动的目的是最大限度地发挥我们工作的影响力，并利用商业化出现的机会。总之，我们将研究一种全球重要的病原体，并制定适用于控制所有细菌的策略。重要的是，这一应用是在人们正在寻找抗生素替代品的时候出现的，采取行动的机会之窗是敞开的。我们已经与我们数据的重要“最终用户”建立了联系，以最大限度地提高我们工作的经济影响。

项目成果

Homologs of the Escherichia coli F Element Protein TraR, Including Phage Lambda Orf73, Directly Reprogram Host Transcription.

• DOI: 10.1128/mbio.00952-22
• 发表时间: 2022-06-28
• 期刊: MBIO
• 影响因子: 6.4
• 作者: Gopalkrishnan, Saumya;Ross, Wilma;Akbari, Madeline S.;Li, Xintian;Haycocks, James R. J.;Grainger, David C.;Court, Donald L.;Gourse, Richard L.
• 通讯作者: Gourse, Richard L.

cAMP Receptor Protein Controls Vibrio cholerae Gene Expression in Response to Host Colonization.

• DOI: 10.1128/mbio.00966-18
• 发表时间: 2018-07-10
• 期刊: mBio
• 影响因子: 6.4
• 作者: Manneh-Roussel J;Haycocks JRJ;Magán A;Perez-Soto N;Voelz K;Camilli A;Krachler AM;Grainger DC
• 通讯作者: Grainger DC

Genome-wide mapping of Vibrio cholerae VpsT binding identifies a mechanism for c-di-GMP homeostasis

霍乱弧菌 VpsT 结合的全基因组图谱确定了 c-di-GMP 稳态机制

• DOI: 10.1101/2021.10.04.463056
• 发表时间: 2021
• 作者: Guest T

Unusually Situated Binding Sites for Bacterial Transcription Factors Can Have Hidden Functionality.

• DOI: 10.1371/journal.pone.0157016
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Haycocks JR;Grainger DC
• 通讯作者: Grainger DC

A dual-function RNA balances carbon uptake and central metabolism in Vibrio cholerae.

• DOI: 10.15252/embj.2021108542
• 发表时间: 2021-12-15
• 期刊: The EMBO journal
• 作者: Venkat K;Hoyos M;Haycocks JR;Cassidy L;Engelmann B;Rolle-Kampczyk U;von Bergen M;Tholey A;Grainger DC;Papenfort K
• 通讯作者: Papenfort K