Identifying ecological factors that drive the evolution of innate versus adaptive immunity in bacteria

识别驱动细菌先天免疫和适应性免疫进化的生态因素

• 批准号: NE/M018350/1
• 负责人: Edze Rients Westra
• 金额: $ 67.02万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FM018350%2F1
• 关键词: Identifying; ecological; factors; drive; evolution

How are we going to deal with bacterial infections if pathogens are resistant to antibiotics? And how do we protect bacteria that are useful for industrial production of cheese and yoghurt against their parasites (bacteriophages, the viruses of bacteria)? These are questions of great societal and economic importance that need to be addressed in the near future. The answer to the first question may well lie in the application of parasites that cause the economic problems in industry that is referred to in the second question. Like all organisms bacteria face infectious diseases caused by parasites (bacteriophages) that abuse host resources for their own benefit. These bacteriophages sometimes cause severe problems in food industry, but can perhaps also be applied to fight bacterial infections in humans, or bacterial infections of crops in agriculture. However, bacteria evolved several mechanisms to acquire immunity against bacteriophages. Understanding how bacteriophage immunity evolves in bacteria is one of the key objectives of my research. I am particularly interested in the evolution of two distinct immune mechanisms: bacterial innate and adaptive immunity. I will test how environmental variables impact on the evolution of either immunity mechanism. This will hopefully lead us to conditions where both immune systems of the bacterial host are ineffective, which will aid the use of bacteriophages to combat bacterial infections. On the other hand, my research will likely also identify conditions where the immune system of bacteria is highly effective, which can then be used in food industry to avoid that bacteria that produce our food (e.g. yoghurt) become infected with bacteriophage, which results in severe economic losses. Hence, my research will reveal how, when and why ecological factors drive the evolution of bacterial immunity against bacteriophages. This information is only one step away from applications in industry, where bacteria need to be protected from bacteriophages. Bioreactors could be designed in such a way that bacterial immunity levels are optimal, which would strongly reduce the frequency of bacteriophage infections and the concomitant economic losses. For the purpose of treating patients that are infected with antibiotic resistant bacterial pathogens, phages can be used as an alternative treatment (phage therapy). In this context, my research will provide clues what the optimal treatment method may be in order to avoid or at least reduce the evolution of bacterial immunity against the bacteriophages. Although phage therapy is not yet used on patients, many believe this to be the medicine of the future and a promising alternative for antibiotics. Nevertheless, phage therapy is already being applied in agriculture, to protect crops from bacterial infections, and in food preservations, for example to avoid contamination of food with pathogenic bacteria. Hence, the knowledge gained from my research can be directly implemented to optimize the procedures of applying bacteriophages to combat unwanted bacteria. Apart from these important applications, my research will also provide fundamental insights into the evolution of immunity mechanisms and how their evolution is affected by ecological factors. This may provide general insights that are also applicable to other systems. For example, it will help us to understand how immune systems evolve in nature and what their importance is in controlling diseases and how they influence the evolution and spread of parasites.

如果病原体对抗生素有抗药性，我们将如何处理细菌感染？我们如何保护用于工业生产奶酪和酸奶的细菌免受寄生虫（噬菌体，细菌病毒）的侵害？这些都是具有重大社会和经济意义的问题，需要在不久的将来加以解决。第一个问题的答案很可能在于寄生虫的应用，这种寄生虫会导致第二个问题中提到的工业经济问题。与所有生物一样，细菌面临着由寄生虫（噬菌体）引起的传染病，这些寄生虫为了自身的利益而滥用宿主资源。这些噬菌体有时会在食品工业中引起严重的问题，但也可能用于对抗人类的细菌感染或农业作物的细菌感染。然而，细菌进化出几种机制来获得针对噬菌体的免疫力。了解噬菌体免疫如何在细菌中进化是我研究的关键目标之一。我对两种不同免疫机制的进化特别感兴趣：细菌先天免疫和适应性免疫。我将测试环境变量如何影响免疫机制的进化。这将有希望引导我们到细菌宿主的两个免疫系统都无效的情况下，这将有助于使用噬菌体来对抗细菌感染。另一方面，我的研究也可能确定细菌免疫系统高度有效的条件，然后可以用于食品工业，以避免生产我们食物（例如酸奶）的细菌感染噬菌体，从而导致严重的经济损失。因此，我的研究将揭示生态因素如何，何时以及为什么驱动细菌对噬菌体的免疫进化。这些信息距离工业应用只有一步之遥，在工业中需要保护细菌免受噬菌体的侵害。生物反应器的设计可以使细菌免疫水平达到最佳，这将大大降低噬菌体感染的频率和随之而来的经济损失。为了治疗感染抗生素耐药细菌病原体的患者，噬菌体可用作替代治疗（噬菌体疗法）。在这种情况下，我的研究将提供最佳治疗方法的线索，以避免或至少减少细菌对噬菌体的免疫力的进化。虽然噬菌体疗法尚未用于患者，但许多人认为这是未来的药物，是抗生素的一种有前途的替代品。尽管如此，噬菌体疗法已经应用于农业，以保护作物免受细菌感染，并用于食品消毒，例如避免食品被病原菌污染。因此，从我的研究中获得的知识可以直接用于优化应用噬菌体对抗有害细菌的程序。除了这些重要的应用外，我的研究还将为免疫机制的进化以及它们的进化如何受到生态因素的影响提供基本见解。这可以提供也适用于其他系统的一般见解。例如，它将帮助我们了解免疫系统在自然界中如何进化、它们在控制疾病方面的重要性以及它们如何影响寄生虫的进化和传播。

项目成果

Regulation of prophage induction and lysogenization by phage communication systems.

• DOI: 10.1016/j.cub.2021.08.073
• 发表时间: 2021-11-22
• 期刊: Current biology : CB
• 作者: Bruce JB;Lion S;Buckling A;Westra ER;Gandon S
• 通讯作者: Gandon S

Bacterial biodiversity drives the evolution of CRISPR-based phage resistance in Pseudomonas aeruginosa

细菌多样性推动铜绿假单胞菌基于 CRISPR 的噬菌体抗性进化

• DOI: 10.1101/586115
• 发表时间: 2019
• 作者: Alseth E

Evolutionary emergence of infectious diseases in heterogeneous host populations.

• DOI: 10.1371/journal.pbio.2006738
• 发表时间: 2018-09
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Chabas H;Lion S;Nicot A;Meaden S;van Houte S;Moineau S;Wahl LM;Westra ER;Gandon S
• 通讯作者: Gandon S

The effect of Quorum sensing inhibitors on the evolution of CRISPR-based phage immunity in Pseudomonas aeruginosa.

• DOI: 10.1038/s41396-021-00946-6
• 发表时间: 2021-08
• 期刊: The ISME journal
• 作者: Broniewski JM;Chisnall MAW;Høyland-Kroghsbo NM;Buckling A;Westra ER
• 通讯作者: Westra ER

Individual bacteria in structured environments rely on phenotypic resistance to phage.

• DOI: 10.1371/journal.pbio.3001406
• 发表时间: 2021-10
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Attrill EL;Claydon R;Łapińska U;Recker M;Meaden S;Brown AT;Westra ER;Harding SV;Pagliara S
• 通讯作者: Pagliara S