Toxin-antitoxin (TA) systems are small genetic elements composed of a toxin gene and its cognate antitoxin that are important for plasmid stabilization (plasmid-encoded) and bacterial virulence (chromosome-encoded). These systems are also related to biofilm and persister cell formations. Pseudomonas aeruginosa is an antibiotic-resistant human pathogen that produces virulence factors modulated by quorum sensing (QS) and can form biofilms. The type II PumAB TA system of pUM505, isolated from a clinical strain of P. aeruginosa , confers plasmid stability. Additionally, the PumA toxin increases P. aeruginosa virulence and is neutralized by the PumB antitoxin. In this study, we determined whether virulence conferred by PumA toxin is regulated by QS. The pum A gene was transferred to P. aeruginosa las I/ rhl I, a mutant strain in the LasI and RhlI QS systems, to analyze the effect on virulence of the transformants. pum A transfer did not increase bacterial virulence in lettuce and Caenorhabditis elegans , suggesting that the virulence conferred by PumA requires QS modulation. pum A mRNA levels drastically decreased in the P. aeruginosa las I/ rhl I (pUC_pumA) strain, suggesting positive regulation of pum A gene expression by QS. Supplementation of the growth medium of P. aeruginosa las I/ rhl I (pUC_pumA) with C4-AHL and 3-oxo-C12-AHL autoinducers increased pum A mRNA levels and restored bacterial virulence, suggesting that both autoinducers complemented the mutations and positively regulated the toxic effects of PumA. This strengthened the hypothesis that QS regulates bacterial virulence conferred by the PumA toxin. Thus, this report establishes an important function of QS in the virulence conferred by plasmid-encoded TA systems in bacterial pathogens.

中文翻译：

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来自质粒编码的 PumAB 毒素-抗毒素系统的 PumA 毒素赋予的毒力受法定人数系统的调节

毒素-抗毒素 (TA) 系统是由毒素基因及其同源抗毒素组成的小型遗传元件，它们对质粒稳定（质粒编码）和细菌毒力（染色体编码）很重要。这些系统还与生物膜和持久细胞形成有关。铜绿假单胞菌是一种耐抗生素的人类病原体，可产生由群体感应 (QS) 调节的毒力因子，并可形成生物膜。从铜绿假单胞菌的临床菌株中分离的 pUM505 的 II 型 PumAB TA 系统赋予质粒稳定性。此外，PumA 毒素会增加铜绿假单胞菌的毒力并被 PumB 抗毒素中和。在这项研究中，我们确定了美洲狮毒素赋予的毒力是否受 QS 调节。pum A 基因被转移到铜绿假单胞菌 las I/rhl I，LasI 和 RhlI QS 系统中的突变菌株，以分析对转化体毒力的影响。pum A 转移不会增加生菜和秀丽隐杆线虫中的细菌毒力，这表明 PumA 赋予的毒力需要 QS 调节。pum A mRNA 水平在铜绿假单胞菌 las I/rhl I (pUC_pumA) 菌株中急剧下降，表明 QS 对 pum A 基因表达的正调控。用 C4-AHL 和 3-oxo-C12-AHL 自诱导剂补充铜绿假单胞菌 las I/rhl I (pUC_pumA) 的生长培养基增加了 pum A mRNA 水平并恢复了细菌毒力，表明这两种自诱导剂补充了突变并正调节美洲狮的毒性作用。这加强了 QS 调节由美洲狮毒素赋予的细菌毒力的假设。因此，