Serum influences the expression of Pseudomonas aeruginosa quorum-sensing genes and QS-controlled virulence genes during early and late stages of growth

In response to diverse environmental stimuli at different infection sites, Pseudomonas aeruginosa, a serious nosocomial pathogen, coordinates the production of different virulence factors through a complicated network of the hierarchical quorum-sensing (QS) systems including the las, rhl, and the 2-alkyl-4-quinolone- related QS systems. We recently showed that at early stages of growth serum alters the expression of numerous P. aeruginosa genes. In this study, we utilized transcriptional analysis and enzyme assays to examine the effect of serum on the QS and QS-controlled virulence factors during early and late phases of growth of the P. aeruginosa strain PAO1. At early phase, serum repressed the transcription of lasI, rhlI, and pqsA but not lasR or rhlR. However, at late phase, serum enhanced the expression of all QS genes. Serum produced a similar effect on the synthesis of the autoinducers 3OC(12)-HSL, C-4-HSL, and HHQ/PQS. Additionally, serum repressed the expression of several QS-controlled genes in the early phase, but enhanced them in the late phase. Furthermore, serum influenced the expression of different QS-positive (vqsR, gacA, and vfr) as well as QS-negative (rpoN, qscR, mvaT, and rsmA) regulatory genes at either early or late phases of growth. However, with the exception of PAO Delta vfr, we detected comparable levels of lasI/lasR expression in PAO1 and PAO1 mutants defective in these regulatory genes. At late stationary phase, serum failed to enhance lasI/lasR expression in PAO Delta vfr. These results suggest that depending on the phase of growth, serum differentially influenced the expression of P. aeruginosa QS and QS-controlled virulence genes. In late phase, serum enhanced the expression of las genes through vfr.