Slinger Betty L, Banerjee Samalee, Chandler Josephine R, Blackwell Helen E
Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, Wisconsin 53706, United States.
Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Ave., Lawrence, Kansas 66045, United States.
ACS Chem Biol. 2024 Dec 20;19(12):2557-2568. doi: 10.1021/acschembio.4c00641. Epub 2024 Dec 5.
Quorum sensing (QS) is a prominent chemical communication mechanism used by common bacteria to regulate group behaviors at high cell density, including many processes important in pathogenesis. There is growing evidence that certain bacteria can use QS to sense not only themselves but also other species and that this crosstalk could alter collective behaviors. In the current study, we report the results of culture-based and coinfection experiments that probe interspecies interactions between the opportunistic pathogens and involving their LuxI/LuxR-type QS circuits. Using a infection model, we show that infections with both species result in poorer host outcomes compared with monoinfections. We use genetic mutants and a transwell infection assay to establish that crosstalk via LuxR-type receptors and signals is important for this coinfection pathogenicity. Using laboratory cocultures with cell-based reporter systems, we show that the RhlR and CepR receptors in and , respectively, can each recognize a QS signal produced by the other species. Lastly, we apply chemical biology to complement our genetic approach and demonstrate the potential to regulate interspecies interactions between the wild-type strains of and through the application of synthetic compounds that modulate RhlR and CepR activities. Overall, this study reveals that interspecies interaction via QS networks is possible between and and that it can contribute to coinfection severity with these two species.
群体感应(QS)是常见细菌用于在高细胞密度下调节群体行为的一种重要化学通讯机制,包括许多在发病机制中重要的过程。越来越多的证据表明,某些细菌不仅可以利用群体感应来感知自身,还能感知其他物种,并且这种种间通讯可能会改变群体行为。在本研究中,我们报告了基于培养和共感染实验的结果,这些实验探究了机会性病原体之间的种间相互作用及其LuxI/LuxR型群体感应回路。使用感染模型,我们发现与单感染相比,两种病原体的共同感染会导致宿主预后更差。我们使用基因敲除突变体和Transwell共培养感染实验来确定通过LuxR型受体和信号进行的种间通讯对于这种共感染致病性很重要。通过基于细胞报告系统的实验室共培养,我们发现,在铜绿假单胞菌和肺炎克雷伯菌中,RhlR和CepR受体分别可以识别另一种细菌产生的群体感应信号。最后,我们应用化学生物学来补充我们的遗传学方法,并证明通过应用调节RhlR和CepR活性的合成化合物来调节铜绿假单胞菌和肺炎克雷伯菌野生型菌株之间种间相互作用的潜力。总体而言,本研究揭示了铜绿假单胞菌和肺炎克雷伯菌之间通过群体感应网络进行种间相互作用是可能的,并且这可能会导致这两种细菌共感染的严重程度增加。