Secretion of Pseudomonas aeruginosa type III cytotoxins is dependent on pseudomonas quinolone signal concentration

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that can, like other bacterial species, exist in antimicrobial resistant sessile biofilms and as free-swimming, planktonic cells. Specific virulence factors are typically associated with each lifestyle and several two-component response regulators have been shown to reciprocally regulate transition between biofilm-associated chronic, and free-swimming acute infections. Quorum sensing (QS) signal molecules belonging to the las and rhl systems are known to regulate virulence gene expression by P. aeruginosa. However the impact of a recently described family of novel quorum sensing signals produced by the Pseudomonas Quinolone Signal (PQS) biosynthetic pathway, on the transition between these modes of infection is less clear. Using clonal isolates from a patient developing ventilator-associated pneumonia, we demonstrated that clinical observations were mirrored by an in vitro temporal shift in isolate phenotype from a non-secreting, to a Type III cytotoxin secreting (TTSS) phenotype and further, that this phenotypic change was PQS-dependent. While intracellular type III cytotoxin levels were unaffected by PQS concentration, cytotoxin secretion was dependent on this signal molecule. Elevated PQS concentrations were associated with inhibition of cytotoxin secretion coincident with expression of virulence factors such as elastase and pyoverdin. In contrast, low concentrations or the inability to biosynthesize PQS resulted in a reversal of this phenotype. These data suggest that expression of specific P. aeruginosa virulence factors appears to be reciprocally regulated and that an additional level of PQS-dependent posttranslational control, specifically governing type III cytotoxin secretion, exists in this species.

Unravelling the Genome-Wide Contributions of Specific 2-Alkyl-4-Quinolones and PqsE to Quorum Sensing in Pseudomonas aeruginosa

“…PQS production has been indirectly linked to the regulation of T3S effector secretion in P . aeruginosa at the post-transcriptional level [42]. Interestingly, the rhl QS system that represses both pqsA and pqsR also negatively regulates exoS [43].…”

Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial

“…It appears that exoU is not associated with the risk for VAP but with its severity. Interestingly, the TTSS is negatively controlled by QS [23,24]. Therefore, inhibition of QS by azithromycin should have potentially increased the expression of type III cytotoxins, and therefore the risk for severe VAP.…”

Characterization of protease IV expression in Pseudomonas aeruginosa clinical isolates

“…The similarity of the piv gene sequence of strain Pear17 to those of strains possessing the exoU gene rather than the exoS gene, corresponding to increased virulence of this low-protease-containing strain, suggests that the piv gene might be part of a genomic island containing other virulence factors that combine with genome modules within this strain to increase virulence. Singh et al (2010) recently suggested a reciprocal regulation of the TTSS and Pseudomonas Quinolone Signal (PQS), both regulated by the las and rhl quorum-sensing systems (Bleves et al, 2005). Furthermore, host defences can disrupt quorum sensing of invading P. aeruginosa (Chun et al, 2004), suggesting a complex interplay of virulence factors and an orchestration of host and pathogen responses during infection, all of which requires further elucidation.…”