Banerjee Samalee, Smalley Nicole E, Saenjamsai Pradtahna, Fehr Anthony R, Dandekar Ajai A, Cabeen Matthew T, Chandler Josephine R
Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.
Department of Microbiology, University of Washington, Seattle, Washington, USA.
J Bacteriol. 2025 Aug 21;207(8):e0004825. doi: 10.1128/jb.00048-25. Epub 2025 Aug 1.
In the opportunistic pathogen , the nitrogen-related phosphotransferase system (PTS) influences multiple virulence behaviors. The PTS is comprised of three enzymes: first PtsP, then the PtsO phosphocarrier, and the final PtsN phosphoacceptor. We previously showed that inactivation enhances LasI-LasR quorum sensing, a system by which regulates genes in response to population density. LasI synthesizes a diffusible autoinducer that binds and activates the LasR receptor, which activates a feedback loop by increasing expression. In this study, we examined the impact of the PTS on quorum sensing. Disruption of increased the expression of some, but not all, tested quorum-controlled genes, including (pyocyanin biosynthesis), (hydrogen cyanide biosynthesis), and, to a lesser extent, (quorum sensing regulator). Expression of these genes remained dependent on LasR and the autoinducer, whether provided endogenously or exogenously. Increased expression in ∆ (or ∆) cells was partly due to the presence of unphosphorylated PtsN, which alone was sufficient to elevate expression. However, we observed residual increases in ∆ or ∆ cells even in the absence of PtsN, suggesting that PtsP and PtsO can regulate gene expression independently of PtsN. Indeed, genetically disrupting the PtsO phosphorylation site impacted gene expression in the absence of PtsN, and transcriptomic evidence suggested that PtsO and PtsN have distinct regulons. Our results expand our view of how the PTS components function both within and apart from the classic phosphorylation cascade to regulate key virulence behaviors in .
often causes severe and difficult-to-treat infections. virulence requires the nitrogen-related phosphotransferase system (PTS), which comprises the phosphocarrier proteins PtsP and PtsO and the final phosphoacceptor, PtsN. The PTS is known to modulate quorum sensing, but little is known about the mechanism of regulation. Here, we examined quorum sensing regulation by the PTS. We showed that the PTS increases quorum sensing-mediated activation of certain genes through the additive effects of both PtsO and PtsN. We also used transcriptomics to determine the regulons of PtsO and PtsN and found that they are largely nonoverlapping. The results position PtsO and PtsN as independent effectors in the PTS and shed new light on virulence regulation in this important pathogen.
在机会性病原体中，氮相关磷酸转移酶系统（PTS）影响多种毒力行为。PTS由三种酶组成：首先是PtsP，然后是PtsO磷酸载体，最后是PtsN磷酸受体。我们之前表明，失活会增强LasI-LasR群体感应，这是一种细菌根据群体密度调节基因的系统。LasI合成一种可扩散的自诱导物，它结合并激活LasR受体，LasR受体通过增加基因表达来激活一个反馈回路。在这项研究中，我们研究了PTS对群体感应的影响。PTS的破坏增加了一些但不是所有测试的群体感应控制基因的表达，包括（绿脓菌素生物合成）、（氰化氢生物合成），以及在较小程度上的（群体感应调节因子）。这些基因的表达仍然依赖于LasR和自诱导物，无论其是内源性提供还是外源性提供。∆（或∆）细胞中表达的增加部分归因于未磷酸化的PtsN的存在，单独的PtsN就足以提高表达。然而，我们观察到即使在没有PtsN的情况下，∆或∆细胞中的表达仍有残余增加，这表明PtsP和PtsO可以独立于PtsN调节基因表达。事实上，在没有PtsN的情况下，基因破坏PtsO的磷酸化位点会影响基因表达，转录组学证据表明PtsO和PtsN有不同的调控子。我们的结果扩展了我们对PTS组件如何在经典磷酸化级联反应之内和之外发挥作用以调节关键毒力行为的认识。
常常引起严重且难以治疗的感染。的毒力需要氮相关磷酸转移酶系统（PTS），该系统由磷酸载体蛋白PtsP和PtsO以及最终的磷酸受体PtsN组成。已知PTS可调节群体感应，但对其调节机制知之甚少。在这里，我们研究了PTS对群体感应 的调节作用。我们表明，PTS通过PtsO和PtsN的加性效应增加群体感应介导的某些基因的激活。我们还使用转录组学来确定PtsO和PtsN的调控子，发现它们在很大程度上不重叠。这些结果将PtsO和PtsN定位为PTS中的独立效应器，并为这种重要病原体的毒力调节提供了新的见解。
