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

如果病原体对抗生素有耐药性，我们将如何应对细菌感染？我们如何保护对奶酪和酸奶工业生产有用的细菌免受寄生虫（噬菌体，细菌的病毒）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，它们会导致第二个问题中提到的工业经济问题。像所有生物一样，细菌面临由寄生虫（噬菌体）引起的传染病，这些寄生虫为了自己的利益滥用宿主资源。这些噬菌体有时会在食品工业中造成严重的问题，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对噬菌体的免疫。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这两种免疫机制的进化。这将有希望引导我们达到细菌宿主的两个免疫系统都无效的情况，这将有助于利用噬菌体来对抗细菌感染。另一方面，我的研究也可能会确定细菌免疫系统非常有效的条件，然后可以在食品工业中使用，以避免生产我们的食物（例如酸奶）的细菌被噬菌体感染，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、何时以及为何驱动细菌对噬菌体的免疫进化。这一信息距离工业应用只有一步之遥，在工业中，细菌需要免受噬菌体的侵害。生物反应器的设计可以使细菌免疫水平达到最佳，这将大大减少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，噬菌体可作为一种替代治疗方法（噬菌体疗法）。在此背景下，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，是抗生素的有希望的替代品。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，以及用于食品保存，例如避免致病菌污染食品。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来对抗有害细菌的程序。除了这些重要的应用之外，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的见解。这可能提供一般的见解，也适用于其他系统。例如，它将帮助我们了解免疫系统在自然界中是如何进化的，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。

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.