Pseudomonas aeruginosa, a harmful nosocomial pathogen associated with cystic fibrosis and burn wounds, encodes for a large number of LysR-type transcriptional regulator proteins. To understand how and why LTTR proteins evolved with such frequency and to establish whether any relationships exist within the distribution we set out to identify the patterns underpinning LTTR distribution in P. aeruginosa and to uncover cluster-based relationships within the pangenome. Comparative genomic studies revealed that in the JGI IMG database alone ~86 000 LTTRs are present across the sequenced genomes (n=699). They are widely distributed across the species, with core LTTRs present in >93 % of the genomes and accessory LTTRs present in <7 %. Analysis showed that subsets of core LTTRs can be classified as either variable (typically specific to P. aeruginosa) or conserved (and found to be distributed in other Pseudomonas species). Extending the analysis to the more extensive Pseudomonas database, PA14 rooted analysis confirmed the diversification patterns and revealed PqsR, the receptor for the Pseudomonas quinolone signal (PQS) and 2-heptyl-4-quinolone (HHQ) quorum-sensing signals, to be amongst the most variable in the dataset. Successful complementation of the PAO1 pqsR - mutant using representative variant pqsR sequences suggests a degree of structural promiscuity within the most variable of LTTRs, several of which play a prominent role in signalling and communication. These findings provide a new insight into the diversification of LTTR proteins within the P. aeruginosa species and suggests a functional significance to the cluster, conservation and distribution patterns identified.

中文翻译：

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比较基因组学揭示 ESKAPE 病原体铜绿假单胞菌中 LysR 型转录调节因子的独特多样化模式

铜绿假单胞菌是一种与囊性纤维化和烧伤创面相关的有害医院病原体，编码大量 LysR 型转录调节蛋白。为了了解 LTTR 蛋白如何以及为何以如此高的频率进化，并确定分布中是否存在任何关系，我们着手识别铜绿假单胞菌中 LTTR 分布的模式，并揭示全基因组内基于簇的关系。比较基因组研究表明，仅在 JGI IMG 数据库中，已测序的基因组中就存在约 86 000 个 LTTR（n = 699）。它们广泛分布在整个物种中，核心 LTTR 存在于 >93% 的基因组中，而辅助 LTTR 则存在于 <7% 的基因组中。分析表明，核心 LTTR 子集可分为可变子集（通常特定于铜绿假单胞菌）或保守子集（发现分布于其他假单胞菌属物种中）。将分析扩展到更广泛的假单胞菌数据库，基于 PA14 的分析证实了多样化模式，并揭示了 PqsR（假单胞菌喹诺酮信号 (PQS) 和 2-庚基-4-喹诺酮 (HHQ) 群体感应信号的受体）也在其中。数据集中变量最大的。使用代表性变体 pqsR 序列对 PAO1 pqsR 突变体的成功互补表明 ，LTTR 的变异程度最大，其中有一些在信号传导和通讯中发挥着重要作用。这些发现为铜绿假单胞菌物种内 LTTR 蛋白的多样化提供了新的见解，并表明其对所识别的簇、保护和分布模式具有功能意义。