Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Apdo, Postal 70228, C. P. 04510, CDMX, Mexico.
Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad 2001, Col. Chamilpa, Cuernavaca, Morelos CP 62210, Mexico.
Microbiology (Reading). 2023 Oct;169(10). doi: 10.1099/mic.0.001401.
is a widespread γ-proteobacterium and an important opportunistic pathogen. The genetically diverse phylogroup 3 strains are characterized by producing the pore-forming ExlA toxin and by their lack of a type III secretion system. However, like all strains of this species, they produce several virulence-associated traits, such as elastase, rhamnolipids and pyocyanin, which are regulated by quorum sensing (QS). The QS response comprises three systems (Las, Rhl and Pqs, respectively) that hierarchically regulate these virulence factors. The Pqs QS system is composed of the PqsR transcriptional factor, which, coupled with the alkyl-quinolones HHQ or PQS, activates the transcription of the operon. The products of the first four genes of this operon produce HHQ, which is then converted to PQS by PqsH, while PqsE forms a complex with RhlR and stabilizes it. In this study we report that mutations affecting the Pqs system are particularly common in phylogroup 3 strains. To better understand QS in phylogroup 3 strains we studied strain MAZ105 isolated from tomato rhizosphere and showed that it contains mutations in the central QS transcriptional regulator, LasR, and in the gene encoding the PqsA enzyme involved in the synthesis of PQS. However, it can still produce QS-regulated virulence factors and is virulent in and mildly pathogenic in the mouse abscess/necrosis model; our results show that this may be due to the expression of from a different PqsR-independent promoter than the promoter. Our results indicate that using anti-virulence therapy based on targeting the PQS system will not be effective against infections by phylogroup 3 strains.
是一种广泛存在的γ-变形菌，也是一种重要的机会致病菌。遗传多样性的 3 型进化枝菌株的特征是产生形成孔的 ExlA 毒素，并且缺乏 III 型分泌系统。然而，与该物种的所有菌株一样，它们产生几种与毒力相关的特征，例如弹性蛋白酶、鼠李糖脂和绿脓菌素，这些特征受群体感应（QS）调节。QS 反应由三个系统（Las、Rhl 和 Pqs，分别）组成，它们按层次调节这些毒力因子。Pqs QS 系统由 PqsR 转录因子组成，该因子与烷基-喹诺酮 HHQ 或 PQS 结合，激活 操纵子的转录。该操纵子的前四个基因的产物产生 HHQ，然后由 PqsH 将其转化为 PQS，而 PqsE 与 RhlR 形成复合物并稳定它。在这项研究中，我们报告了影响 Pqs 系统的突变在 3 型进化枝菌株中特别常见。为了更好地了解 3 型进化枝菌株中的 QS，我们研究了从番茄根际分离的 MAZ105 菌株，结果表明它在中央 QS 转录调节剂 LasR 和参与 PQS 合成的 PqsA 酶基因中都发生了突变。然而，它仍然可以产生 QS 调节的毒力因子，并且在 和小鼠脓肿/坏死模型中具有毒力；我们的结果表明，这可能是由于来自与 启动子不同的 PqsR 独立启动子的 表达所致。我们的结果表明，基于针对 PQS 系统的抗毒力治疗针对 3 型进化枝菌株的感染可能不会有效。
