Asif Azka, Iftikhar Anam, Hamood Abdul, Colmer-Hamood Jane A, Qaisar Uzma
School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
Microb Pathog. 2019 Feb;127:288-295. doi: 10.1016/j.micpath.2018.12.001. Epub 2018 Dec 4.
Paerucumarin synthesized by pvc operon pvcABCD is an iron binding molecule which modulates biofilm formation in Pseudomonas aeruginosa but its direct function in bacterial pathogenesis needs further investigation. pvcA synthesizes isonitrile functionalized tyrosine (IFT) which is converted to mature paerucumarin by the proteins encoded by pvcB, pvcC and pvcD genes. Interruption of pvcB in MPAO1 resulted in accumulation of IFT as it cannot be converted to mature molecule. The MPAO1 pvcB mutant (PW4832) showed enhanced swarming motility, while complementation with plasmid pLL2 carrying pvcB reduced swarming motility. Enhanced levels of rhlA expression and rhamnolipid production were observed in PW4832 compared to the parent strain. Overexpression of ptxR, the positive regulator of pvcABCD, in PW4832 caused accumulation of more IFT and further elevated the level of rhlA expression. Expression of the quorum sensing system transcriptional activators lasR and rhlR, as well as the synthase genes lasI and rhlI, was enhanced in PW4832 compared to MPAO1, as was PQS accumulation. Exogenously added IFT, but not paerucumarin, enhanced the production of rhamnolipids in P. aeruginosa. These results suggest that IFT enhances swarming motility in P. aeruginosa either directly by enhancing rhamnolipid production or indirectly through modulation of the quorum sensing systems. This is the first report assigning an independent function to IFT in P. aeruginosa.
由pvc操纵子pvcABCD合成的对羟基苯乙酮香豆素是一种铁结合分子，它可调节铜绿假单胞菌生物膜的形成，但其在细菌致病机制中的直接功能仍需进一步研究。pvcA合成异腈官能化酪氨酸（IFT），后者由pvcB、pvcC和pvcD基因编码的蛋白质转化为成熟的对羟基苯乙酮香豆素。MPAO1中pvcB的中断导致IFT积累，因为它无法转化为成熟分子。MPAO1 pvcB突变体（PW4832）表现出增强的群体运动性，而用携带pvcB的质粒pLL2进行互补则降低了群体运动性。与亲本菌株相比，在PW4832中观察到rhlA表达水平和鼠李糖脂产量增加。pvcABCD的正调控因子ptxR在PW4832中的过表达导致更多IFT积累，并进一步提高rhlA表达水平。与MPAO1相比，PW4832中群体感应系统转录激活因子lasR和rhlR以及合成酶基因lasI和rhlI的表达增强，PQS积累也是如此。外源添加IFT而非对羟基苯乙酮香豆素可增强铜绿假单胞菌中鼠李糖脂的产生。这些结果表明，IFT通过增强鼠李糖脂的产生直接或通过调节群体感应系统间接增强铜绿假单胞菌的群体运动性。这是首次报道IFT在铜绿假单胞菌中具有独立功能。
