Yuan Min, Qiu Huifang, Zhou Xiaoqing, Dai Weijun
Integrative Microbiology Research Center, College of Plant Protection, South China Agricultural University, Guangzhou, China.
PLoS Pathog. 2025 Apr 15;21(4):e1013046. doi: 10.1371/journal.ppat.1013046. eCollection 2025 Apr.
Social interactions substantially influence the dynamics and functions of microbial communities. Cooperative behaviors serve to benefit populations, yet they are often exploited by cheating cells, thus creating a conflict between individuals in the microbial population. However, the underlying mechanisms by which cooperative behaviors are stabilized are incompletely elucidated. Here, we used quorum sensing (QS) as a model of cooperation, and functionally studied QS regulator LasR variant strains in the context of cooperative behaviors. We found that a LasR228 variant strain, bearing a non-conserved substitution in LasR, exhibited minimal LasR-dependent phenotypes. However, the function of this LasR228 variant strain was restored by inactivation of the transcriptional repressor PsdR, and the phenotypes of this variant strain were similar to the parental strain. Furthermore, we illustrate a post-transcriptional regulatory mechanism responsible for the activation of the LasR228 variant. Unlike LasR228, the PsdR-null-LasR228 strain demonstrated cooperative behaviors in competition with the LasR-null strain. Since psdR mutations precede the emergence of LasR variants in the evolution of P. aeruginosa using casein broth, this PsdR-mediated cooperative mechanism serves as an anticipatory control against potential cheating LasR variant strains. Additionally, our cell-killing assay showed that the cooperative PsdR-null-LasR228 strain was associated with increased bacterial pathogenicity to eukaryotic host cells. In conclusion, our study reveals the functional plasticity of LasR variants, which can be modulated by secondary mutations, affecting cooperation and conflict within populations. Our identification of a novel cooperative molecular mechanism offers insight into the maintenance of cooperation within microbial communities.
社会互动极大地影响微生物群落的动态和功能。合作行为有助于群体受益，但它们常常被作弊细胞利用，从而在微生物群体中的个体之间产生冲突。然而，合作行为得以稳定的潜在机制尚未完全阐明。在这里，我们使用群体感应（QS）作为合作模型，并在合作行为的背景下对QS调节因子LasR变异菌株进行了功能研究。我们发现，LasR228变异菌株在LasR中有一个非保守取代，表现出最小的LasR依赖性表型。然而，通过转录阻遏物PsdR的失活，该LasR228变异菌株的功能得以恢复，且该变异菌株的表型与亲本菌株相似。此外，我们阐述了一种负责激活LasR228变异体的转录后调控机制。与LasR228不同，PsdR缺失的LasR228菌株在与LasR缺失菌株的竞争中表现出合作行为。由于在使用酪蛋白肉汤的铜绿假单胞菌进化过程中psdR突变先于LasR变异体出现，这种PsdR介导的合作机制作为一种对潜在作弊LasR变异菌株的预期控制。此外，我们的细胞杀伤试验表明，具有合作性的PsdR缺失的LasR228菌株与对真核宿主细胞的细菌致病性增加有关。总之，我们的研究揭示了LasR变异体的功能可塑性，其可通过二次突变进行调节，影响群体内的合作与冲突。我们对一种新型合作分子机制的鉴定为深入了解微生物群落内合作关系的维持提供了思路。
