phz1 contributes much more to phenazine‐1‐carboxylic acid biosynthesis than phz2 in Pseudomonas aeruginosa rpoS mutant

Abstract

Pseudomonas aeruginosa PAO1, a common opportunistic bacterial pathogen, contains two phenazine-biosynthetic operons, phz1 (). Each of two operons can independently encode a set of enzymes involving in the biosynthesis of phenazine-1-carboxylic acid. As a global transcriptional regulator, RpoS mediates a lot of genes involving secondary metabolites biosynthesis in many bacteria. In an other previous study, it was reported that RpoS deficiency caused overproduction of pyocyanin, a derivative of phenazine-1-carboxylic acid in P. aeruginosa PAO1. But it is not known how RpoS mediates the expression of each of two phz operons and modulates phenazine-1-carboxylic acid biosynthesis in detail. In this study, by deleting the rpoS gene in the mutant PNΔphz1 and the mutant PNΔphz2, we found that the phz1 operon contributes much more to phenazine-1-carboxylic acid biosynthesis than the phz2 operon in the absence of RpoS. With the construction of the translational and transcriptional fusion vectors with the truncated lacZ reporter gene, we demonstrated that RpoS negatively regulates the expression of phz1 and positively controls the expression of phz2, and the regulation of phenazine-1-carboxylic acid biosynthesis mediated by RopS occurs at the posttranscriptional level, not at the transcriptional level. Obviously, two copies of phz operons and their differential expression mediated by RpoS might help P. aeruginosa adapt to its diverse environments and establish infection in its hosts. K E Y W O R D S P. aeruginosa PN, phenazine-1-carboxylic acid, phz1, phz2, RpoS

Treatment with paeoniflorin increases lifespan of Pseudomonas aeruginosa infected Caenorhabditis elegans by inhibiting bacterial accumulation in intestinal lumen and biofilm formation

“…In P. aeruginosa , PelA and PelB can organize a modification and secretion complex, which is essential for Pel polysaccharide-dependent biofilm formation ( Marmont et al, 2017 ). PhzA contributed to the production of phenazine pyocyanin, which is important for P. aeruginosa biofilm formation ( Das et al, 2015 ; Sun et al, 2019 ). P. aeruginosa uses quorum sensing to coordinate their biofilm formation, and lasB and lasR are quorum sensing genes ( Ruffin et al, 2016 ).…”

The transcriptional regulators of virulence for Pseudomonas aeruginosa: Therapeutic opportunity and preventive potential of its clinical infections

“… 31 We and our collaborators have characterized eight regulators (VqsR, VqsM, AlgR, CdpR, CysB, RsaL, AnvM and RpoN) and elucidated their molecular pathogenic mechanisms. 25 , 27 , 28 , 32 , 33 , 34 , 35 , 36 A genomic virulence-associated network containing 20 key TFs and their targets is mapped, providing an online analysis platform for peer researchers. 26 An online regulatory-interaction database of P. aeruginosa , named RegulomePA, is also developed.…”

“…We and our collaborators have determined the direct binding sites of eight QS-related regulators, VqsR, VqsM, AlgR, CdpR, RsaL, CysB, AnvM and RpoN. 25 , 27 , 28 , 32 , 33 , 34 , 35 , 36 The functions of these regulators overlap with other virulence-related pathways. For instance, VqsM simultaneously mediates Las-QS, the T3SS and antibiotic resistance by binding to the promoters of lasI , exsA, and nfxB , respectively.…”

“… 61 RpoS inhibits the expression of phzA1 but activates the expression of phzA2 at the post-transcriptional level, which might be due to the diverse host environments. 36 Because the production of pyocyanin is regulated by QS, the crosstalk among multiple pyocyanin-related regulators is common in P. aeruginosa 's regulatory network. For instance, LasR, RhlR, RsaL, BfmR, CzcR, PtxR and QteE share their targets in the QS, T3SS and T6SS.…”

Data_Sheet_1.DOCX

“…Since PsrA is a known repressor of fadE (PA0506) expression, its overexpression could lead to the accumulation of acyl-CoA, which in turn promotes the synthesis of PQS and pyocyanin (Wells et al, 2017). Another potential factor is the general stress sigma factor RpoS, which downregulates phz1 expression while upregulating phz2 expression (Sun et al, 2019). An rpoS deletion mutant exhibited enhanced pyocyanin production (Suh et al, 1999), suggesting that PsrAmediated rpoS downregulation may contribute to increased pyocyanin production.…”