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Gene duplication often provides selective advantages for the survival of microorganisms in adapting to varying environmental conditions.  P .  aeruginosa  PAO1 possesses two seven-gene operons [ phz1  ( phzA1B1C1D1E1F1G1 ) and  phz2  ( phzA2B2C2D2E2F2G2 )] that are involved in the biosynthesis of phenazine-1-carboxylic acid and its derivatives. Although the two operons are highly homologous and their functions are well known, it is unclear how the two  phz  operons coordinate their expressions to maintain the phenazine biosynthesis. By constructing single and double deletion mutants of the two  phz  operons, we found that the  phz1 -deletion mutant produced the same or less amount of phenazine-1-carboxylic acid and pyocyanin in GA medium than the  phz2- knockout mutant while the  phz1 - phz2  double knockout mutant did not produce any phenazines. By generating  phzA1  and  phzA2  translational and transcriptional fusions with a truncated  lacZ  reporter, we found that the expression of the  phz1  operon increased significantly at the post-transcriptional level and did not alter at the transcriptional level in the absence of the  phz2  operon. Surprisingly, the expression the  phz2  operon increased significantly at the post-transcriptional level and only moderately at the transcriptional level in the absence of the  phz1  operon. Our findings suggested that a complex cross-regulation existed between the  phz1  and  phz2  operons. By mediating the upregulation of one  phz  operon expression while the other was deleted, this crosstalk would maintain the homeostatic balance of phenazine biosynthesis in  P .  aeruginosa  PAO1.

Cross-Regulation between the phz1 and phz2 Operons Maintain a Balanced Level of Phenazine Biosynthesis in Pseudomonas aeruginosa PAO1