Abstract

Adaptation to environments with constant fluctuations imposes challenges that are only overcome with sophisticated strategies that allow bacteria to perceive environmental conditions and develop an appropriate response. The gastrointestinal environment is a complex ecosystem that is home to trillions of microorganisms. Termed microbiota, this microbial ensemble plays important roles in host health and provides colonization resistance against pathogens, although pathogens have evolved strategies to circumvent this barrier. Among the strategies used by bacteria to monitor their environment, one of the most important are the sensing and signalling machineries of two-component systems (TCSs), which play relevant roles in the behaviour of all bacteria. Salmonella enterica is no exception, and here we present our current understanding of how this important human pathogen uses TCSs as an integral part of its lifestyle. We describe important aspects of these systems, such as the stimuli and responses involved, the processes regulated, and their roles in virulence. We also dissect the genomic organization of histidine kinases and response regulators, as well as the input and output domains for each TCS. Lastly, we explore how these systems may be promising targets for the development of antivirulence therapeutics to combat antibiotic-resistant infections.

摘要

对不断波动的环境的适应带来了挑战，只有通过复杂的策略才能克服这些挑战，这些策略使细菌能够感知环境条件并做出适当的反应。胃肠道环境是一个复杂的生态系统，是数万亿微生物的家园。这种微生物群被称为微生物群，在宿主健康中起着重要作用，并提供对病原体的定殖抗性，尽管病原体已经进化出绕过这一障碍的策略。在细菌用于监测其环境的策略中，最重要的策略之一是双组分系统 (TCS) 的传感和信号传递机制，它们在所有细菌的行为中都发挥着相关作用。沙门氏菌也不例外，在这里我们将介绍我们目前对这种重要的人类病原体如何将 TCS 作为其生活方式不可或缺的一部分的理解。我们描述了这些系统的重要方面，例如所涉及的刺激和反应、调节的过程以及它们在毒力中的作用。我们还剖析了组氨酸激酶和反应调节器的基因组组织，以及每个 TCS 的输入和输出域。最后，我们探讨了这些系统如何成为开发抗病毒疗法以对抗抗生素耐药性感染的有希望的目标。