Pseudomonas aeruginosa mutations in lasI and rhlI quorum sensing systems result in milder chronic lung infection

Abstract

To understand the importance of quorum sensing in chronic Pseudomonas aeruginosa lung infection, the in vivo pathogenic effects of the wild-type P. aeruginosa PAO1 and its double mutant, PAO1 lasI rhlI, in which the signalgenerating parts of the quorum sensing systems are defective were compared. The rat model of P. aeruginosa lung infection was used in the present study. The rats were killed on days 3, 7, 14 and 28 after infection with the P. aeruginosa strains. The results showed that during the early stages of infection, the PAO1 double mutant induced a stronger serum antibody response, higher production of pulmonary interferon γ, and more powerful blood polymorphonuclear leukocyte (PMN) chemiluminescence compared to its wild-type counterpart. On days 14 and 28 post-infection, significantly milder lung pathology, a reduction in the number of mast cells present in the lung foci, a reduced number of lung bacteria, and minor serum IgG and IgG1 responses but increased lung interferon γ production were detected in the group infected with the PAO1 double mutant when compared with the PAO1-infected group. Delayed immune responses were observed in the PAO1-infected group and they might be associated with the production of virulence factors that are controlled by the quorum sensing systems. The conclusion of this study is that functional lasI and rhlI genes of P. aeruginosa PAO1 play a significant role during lung infection.

Pseudomonas aeruginosa las and rhl quorum-sensing systems are important for infection and inflammation in a rat prostatitis model

“…aeruginosa infections have been generated in lung models where Ps. aeruginosa is implanted in agar beads in order to establish chronic infections (Wu et al, 2001). Foreign-body models in the lung have produced reproducible pathology-mimicking mucosal disease (Cash et al, 1979;Gallant et al, 2000;Lindsey et al, 2008;Pedersen et al, 1990); however, there have been a number of reports identifying problems with foreign-body models, including bypassing initial Ps.…”

“…aeruginosa virulence has been shown in numerous model systems. These include the Caenorhabditis elegans model (Tan et al, 1999), the acute pneumonia model (Pearson et al, 2000), and the chronic pneumonia agar bead model (Wu et al, 2001). Since the absence of quorum sensing reduced virulence in all models, including the lung model, we believed that quorum sensing may likewise affect the severity of prostate disease.…”

“…In addition, to assess the role of quorum sensing, we used the Ps. aeruginosa PAO1 lasI rhlI double mutant PAO-JP2 (Pearson et al, 1997), utilized in previous studies (Wu et al, 2001), to infect the rat prostate. The resulting inflammatory response and tissue damage were compared between PAO-JP2 and its isogenic WT PAO1 parent at 2, 8 and 12 days postinfection (p.i.)…”

Proteome analysis of extracellular proteins regulated by the las and rhl quorum sensing systems in Pseudomonas aeruginosa PAO1

“…Mutants lacking genes of the las and/or rhl systems are significantly less virulent towards host cells (Tang et al, 1996;Wu et al, 2001), and this appears to be independent of surface colonization (Reimmann et al, 2002). As QS is celldensity-dependent, regulation of virulence factors by this mechanism may allow the organism to mount an attack only when the number of cells present is sufficient to overwhelm the host.…”

P. aeruginosa Quorum Sensing System and the Experimental Model of Chronic Respiratory Infection: Scientific Letter

“…In the chro nic pul mo nary in fec ti on mo del de ve lo ped by Ima mura et al 23 by using QS wild type (PA O1) and thre e QS mu tant stra ins (∆la sI, ∆la sI/∆rhlI, ∆rhlI), it is sta ted that the QS mu tant stra ins can be era di ca ted from lungs mo re ef fec ti vely com pa red to wild-type stra ins, the re fo re they ca u se less da ma ge to the lungs. Wu et al 24 de ve lo ped P. ae ru gi no sa pne moni a in rats by using PA O1 and mu tant PA O JP2 (∆la sI/∆rhlI) stra ins. In the early sta ges of in fec ti on, re se arc hers ob ser ved con si de rably fas ter and stronger im mu ne res pon se aga inst mu tant stra in, lar ger amo unt of pul mo nary IFN-g, and mo re po wer ful res pon se of poly morp ho nuc le er le u kocy tes as well as mo re ra pid an ti body res pon se, and they conc luded that func ti o nal la sI and rhlI ge nes ha ve sig nifi cant ro les in the se ve rity of pul mo nary in fec ti ons.…”