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

Abstract

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 3OC12-HSL, C4-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 PAOΔvfr, 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 PAOΔvfr. 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.

Albumin Inhibits Pseudomonas aeruginosa Quorum Sensing and Alters Polymicrobial Interactions

“…Taken together, these data demonstrated that albumin impacts P. aeruginosa QS; however, while the Las and Rhl systems are repressed by albumin, the PQS system was stimulated. Our results are consistent with those of Kruzcek et al (32), who reported that pyocyanin and PQS were increased in the presence of serum at late stages of P. aeruginosa growth. Thus, while pqsA mutants are attenuated in their ability to kill S. aureus, this effect does not appear to be due to a reduction in pyocyanin or the expression of pqsA.…”

During bacteremia, Pseudomonas aeruginosa PAO1 adapts by altering the expression of numerous virulence genes including those involved in quorum sensing

“…Thus, whole blood and serum may differentially regulate the expression of PAO1 QS genes at early and late stages of growth through one or more of these regulators. We previously showed that ABS significantly reduced the expression of the P. aeruginosa global regulator vfR at early stages of growth of PAO1 but enhanced it at late stages of growth [48]. However, in this study, vfR expression at 4 h of PAO1 growth post-inoculation was essentially unchanged in WBHV and LBBS (Fig 8A and 8B).…”

Major Transcriptome Changes Accompany the Growth of Pseudomonas aeruginosa in Blood from Patients with Severe Thermal Injuries

“…We recently showed that serum influences the expression of different P . aeruginosa genes [ 54 ]. During the growth of P .…”

“…During the growth of P . aeruginosa in LB broth containing 10% serum from healthy volunteers, the expression of QS genes followed a unique pattern in which the genes were repressed at early stages of growth (4 h post-inoculation, OD 600 1.0–1.2) but enhanced at late stages of growth (16 h post-inoculation, OD 600 3.0–4.0) [ 54 ]. Due to the extensive RBC lysis in PA14 blood cultures after 10 h, we did not harvest PA14 cells at late stages of growth.…”