GCR: Collaborative Research: Plasma-Biofilm Interactions at the Intersection of Physics, Chemistry, Biology and Engineering

在大气压下运行的低温等离子体--电离气体--是活性氧和氮物种(RON)的丰富来源。等离子体产生的RON具有对抗抗菌素耐药细菌的能力，并作为一种新的癌症治疗方法。氧化还原过程在细胞生命周期中起着重要作用，是有氧生物代谢的驱动力。等离子体诱导细胞内的氧化还原化学可能调节这些过程。该项目将研究等离子体控制细菌生物膜协调功能群落的能力。物理去除生物膜可能极其困难，而且由于多管齐下的生物膜防御系统，抗生素和局部去污产品在很大程度上是无效的。由于生物膜的广泛用途和影响，从环境工程到生物医学应用，生物膜的控制已经成为一个巨大的社会挑战。例如，生物膜引起的腐蚀是世界航运业面临的一个严重问题。生物被膜和抗菌素耐药性也是食品工业和医药行业的主要问题。抗菌素耐药性预计将成为2050年的头号健康问题，美国疾病控制和预防中心报告称，在美国，每15分钟就有一人死于抗生素无法有效治疗的感染。尽管生物膜的后果通常被认为是负面的，但生物膜细菌也被广泛用于生物反应器，其有益应用范围从水修复到能量收集。该项目将等离子体科学、微生物学和工程学方面的几个研究进展--每个研究进展本身都具有重要意义--结合成一个收敛的、变革性的项目，以研究基本的等离子体诱导的生物膜过程。该项目的目标是发展了解等离子体对活细胞群落的影响所需的科学。等离子体处理生物体可产生非局部效应和全身反应，目前尚不清楚。在复杂的生物体中，例如动物模型，很难对单个细胞的初始血浆剂量进行量化，也很难诊断暴露的后果--动物模型的组成部分太过相互关联。拟议的研究将通过发展对生物膜内等离子体相互作用的基本了解所需的科学来解决量化等离子体对生物体影响的迫切需要--生物膜是一种更简单的有机体交流系统，允许进行诊断和建模。此外，模式生物被膜细菌(例如铜绿假单胞菌)在基因上是易受控制的，有助于在分子水平上详细研究等离子体诱导的影响。这将通过研究等离子体处理后的生物膜相关细菌细胞的生物反应以及它们在细胞外环境中的细胞间通讯来实现对等离子体系统效应的理解。该项目将发展这一新的和融合的研究前沿，结合等离子体科学、微生物学和最新的打印方法，使用生物膜作为模型系统。虽然该项目最初的重点是全球生物膜对等离子体处理的反应，但该项目将推进等离子体和3D打印前沿，以开发高度受控的空间分辨率实验，最终能够处理生物膜中的单个细菌细胞，并跟踪相关的本地和非本地生物影响。这项研究的社会效益将是能够控制生物膜的生长和特征--例如，在不需要的地方消除生物膜，或者在生物膜是理想的产品时促进生物膜的增殖。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Low temperature plasmas – ionized gases – operating at atmospheric pressure are a copious source of reactive oxygen and nitrogen species (RONS). Plasma-produced RONS have the ability to combat antimicrobial resistant bacteria and serve as a novel approach to cancer treatment. Reduction-oxidation (redox) processes play a major role in the cellular life cycle and are the metabolic driving force for aerobic biology. Plasma-induced redox chemistry in cells can potentially regulate these processes. This project will investigate the capability of plasma for control of biofilms – coordinated functional communities of bacteria. Physically removing biofilms can be extremely difficult, and antibiotics and topical decontamination products are largely ineffective due to multipronged biofilm defenses. The control of biofilms has become a grand societal challenge due to their exceptionally broad range of use and impact, from environmental engineering to biomedical applications. As an example, biofilm induced corrosion is a severe problem for world maritime industries. Biofilms and antimicrobial resistance are also major issues in the food industry and in medicine. Antimicrobial resistance is predicted to become the number one health problem in 2050 and the Centers for Disease Control and Prevention reports that every 15 minutes one person in the US dies because of an infection that antibiotics cannot treat effectively. Although the consequences of biofilms are typically thought of as being negative, biofilm bacteria are also extensively used in bioreactors with beneficial applications ranging from water remediation to energy harvesting. This project combines several research advances in plasma science, microbiology and engineering – each significant in their own right – into a convergent, transformative project to investigate fundamental plasma-induced biofilm processes.The goal of the project is to develop the science required to understand the impact of plasmas on communities of living cells. Plasma treatment of organisms can produce non-local effects and systemic responses which are currently not understood. In complex organisms, such as animal models, it is difficult to quantify both the initiating plasma dose to individual cells and to diagnose consequences of the exposure – components of animal models are simply too inter-related. The proposed research will address the critical need to quantify plasma effects on organisms by developing the science required to obtain a fundamental understanding of plasma interactions within a biofilm – a simpler system of communicating organisms that allows access to diagnostics and modeling. Furthermore, model biofilm bacteria (e.g. Pseudomonas aeruginosa) are genetically tractable, lending themselves to detailed studies of plasma-induced effects at a molecular level. This improvement in understanding of systemic effects of plasma will be accomplished by investigating the biological response of plasma-treated, biofilm-associated, bacterial cells and their intercellular communication through the extra-cellular environment. The project will develop this new and convergent research frontier, combining plasma science, microbiology, and state-of-the-art printing methodologies, using biofilms as a model system. While initially focusing on global biofilm response to the plasma treatment, the project will advance plasma and 3D printing frontiers to develop highly controlled spatially-resolved experiments that could ultimately enable the treatment of a single bacterium cell in a biofilm and track the associated local and non-local biological impacts. The societal benefits of this research will be the ability to manipulate the growth and character of biofilms – for example, to eliminate biofilms where they are not desired, or to enhance their proliferation where biofilms are a desired product.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.