Moonlighting chaperone activity of the enzyme PqsE contributes to RhlR-controlled virulence of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a major cause of nosocomial infections and also leads to severe exacerbations in cystic fibrosis or chronic obstructive pulmonary disease. Three intertwined quorum sensing systems control virulence of P. aeruginosa, with the rhl circuit playing the leading role in late and chronic infections. The majority of traits controlled by rhl transcription factor RhlR depend on PqsE, a dispensable thioesterase in Pseudomonas Quinolone Signal (PQS) biosynthesis that interferes with RhlR through an enigmatic mechanism likely involving direct interaction of both proteins. Here we show that PqsE and RhlR form a 2:2 protein complex that, together with RhlR agonist N-butanoyl-L-homoserine lactone (C4-HSL), solubilizes RhlR and thereby renders the otherwise insoluble transcription factor active. We determine crystal structures of the complex and identify residues essential for the interaction. To corroborate the chaperone-like activity of PqsE, we design stability-optimized variants of RhlR that bypass the need for C4-HSL and PqsE in activating PqsE/RhlR-controlled processes of P. aeruginosa. Together, our data provide insight into the unique regulatory role of PqsE and lay groundwork for developing new P. aeruginosa-specific pharmaceuticals.

Establishment of Pediatric Medication Therapy Management: A Proposed Model.

Ongoing healthcare reform calls for increased accessibility, enhanced delivery, and improved quality of healthcare. Children and adolescents are experiencing a rise in the prevalence in chronic diseases leading to an increased utilization of medications. The increased use of chronic medications can lead to more medication errors or adverse drug events, particularly in children and adolescents using multiple chronic medications. These ongoing changes expand opportunities for a pharmacist to become further integrated in the inter-professional healthcare delivery for pediatric patients, particularly in an ambulatory or community setting. To date, a systemic process for the provision of medication therapy management (MTM) services in pediatric patients has not been elucidated. The purpose of this paper is to describe a proposed model for delivering pediatric MTM. Furthermore, based on the available literature related to pediatric patients at risk for medication errors, adverse drug reactions, and subsequently-increased utilization of emergency departments and hospitalizations, a set of criteria is proposed for further research investigation.