Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, México.
Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, México.
J Bacteriol. 2021 Feb 8;203(5). doi: 10.1128/JB.00475-20.
is a major nosocomial pathogen that presents high-level resistance to antibiotics. Its ability to cause infections relies on the production of multiple virulence factors. Quorum sensing (QS) regulates the expression of many of these virulence factors through three QS systems: Las, Rhl, and PQS. The Las system positively regulates the other two systems, so it is at the top of a hierarchized regulation. Nevertheless, clinical and environmental strains that lack a functional Las system have been isolated, and, surprisingly, some of them still have the ability to produce virulence factors and infect animal models, so it has been suggested that the hierarchy is flexible under some conditions or with atypical strains. Here, we analyze the PAO1 type strain and its Δ-derived mutant and report, for the first time, a growth condition (phosphate limitation) where LasR absence has no effect either on virulence factor production or on the gene expression profile, in contrast to a condition of phosphate repletion where the LasR hierarchy is maintained. This work provides evidence on how the QS hierarchy can change from being a strictly LasR-dependent to a LasR-independent RhlR-based hierarchy under phosphate limitation even in the PAO1 type strain. is an important pathogen, considered a priority for the development of new therapeutic strategies. An important approach to fight its infections relies on blocking quorum sensing. The Las system is the main regulator of the quorum-sensing response, so many research efforts aim to block this system to suppress the entire response. In this work, we show that LasR is dispensable in a phosphate-limited environment in the PAO1 type strain, which has been used to define the quorum-sensing response hierarchy, and that under this condition RhlR is at the top of the regulation hierarchy. These results are highly significant, since phosphate limitation represents a similar environment to the one that faces when establishing infections.
铜绿假单胞菌是一种主要的医院病原体，对抗生素表现出高水平的耐药性。它引起感染的能力依赖于多种毒力因子的产生。群体感应（QS）通过三个 QS 系统：Las、Rhl 和 PQS 调节这些毒力因子的表达。Las 系统正向调节另外两个系统，因此它处于分层调节的顶端。然而，已经分离出缺乏功能 Las 系统的临床和环境菌株，令人惊讶的是，其中一些菌株仍然具有产生毒力因子和感染动物模型的能力，因此有人提出在某些条件下或具有非典型菌株时，这种层次结构是灵活的。在这里，我们分析了 PAO1 型菌株及其衍生的 Δ突变体，并首次报告了一种生长条件（磷酸盐限制），在这种条件下，LasR 的缺失既不会影响毒力因子的产生，也不会影响基因表达谱，与磷酸盐补充条件形成对比，在磷酸盐补充条件下，LasR 层次结构得以维持。这项工作提供了证据，证明在磷酸盐限制下，QS 层次结构如何从严格依赖 LasR 转变为依赖 LasR 的 RhlR 层次结构，即使在 PAO1 型菌株中也是如此。是一种重要的病原体，被认为是开发新治疗策略的优先事项。对抗其感染的一个重要方法是阻断群体感应。Las 系统是群体感应反应的主要调节剂，因此许多研究工作旨在阻断该系统以抑制整个反应。在这项工作中，我们表明，LasR 在 PAO1 型菌株的磷酸盐限制环境中是可有可无的，这种环境已被用于定义群体感应反应层次结构，并且在这种条件下，RhlR 处于调节层次结构的顶端。这些结果非常重要，因为磷酸盐限制代表了铜绿假单胞菌在建立感染时所面临的类似环境。
