Drug resistant infections are an increasing problem world-wide, responsible for an estimated 700,000 annual mortalities. The use of antibiotics to treat such infections has resulted in the development of resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). One potential alternative strategy for treating drug resistant bacterial infections is to inhibit the production of toxins, thereby making the bacteria less harmful to the host, a so called “anti-virulence” approach. In MRSA, the agr quorum sensing system is one of the major regulators of toxin production, and quorum sensing inhibitors that target this system are a promising anti-virulence strategy. With this study, we developed a method that enables the activity of quorum sensing inhibitors to be measured using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS). This method is an improvement over existing methods because it can be employed to distinguish antimicrobial activity from quorum sensing inhibition activity based on the UPLC-MS data. This is possible by simultaneously tracking production of metabolites regulated by the agr quorum sensing system (AIP-I and formylated δ-toxin) and a metabolite that appears not to be agr regulated under the conditions of this study (aureusimine B). The newly developed method provides more nuanced indication of how metabolite production changes over time and in response to quorum sensing or growth inhibition than is possible with commonly employed spectroscopic methods.

抗药性感染是世界范围内日益严重的问题，估计每年造成 700,000 人死亡。使用抗生素治疗此类感染导致了耐药细菌病原体的产生，例如耐甲氧西林金黄色葡萄球菌(MRSA)。治疗耐药细菌感染的一种潜在替代策略是抑制毒素的产生，从而降低细菌对宿主的危害，即所谓的“抗毒力”方法。在 MRSA 中，agr群体感应系统是毒素产生的主要调节器之一，针对该系统的群体感应抑制剂是一种很有前途的抗毒力策略。通过这项研究，我们开发了一种方法，可以使用超高效液相色谱与质谱联用 (UPLC-MS) 测量群体感应抑制剂的活性。该方法是对现有方法的改进，因为它可用于根据 UPLC-MS 数据区分抗菌活性和群体感应抑制活性。这可以通过同时跟踪受agr群体感应系统（AIP-I 和甲酰化 δ-毒素）调节的代谢物和似乎不是agr的代谢物的产生来实现。在本研究的条件下进行调节（金黄色亚胺 B）。与常用光谱方法相比，新开发的方法提供了更细致的指示，说明代谢物产生如何随时间变化以及如何响应群体感应或生长抑制。